TWiV 1371: How to Bat Away Marburg Virus

0:00This Week in Virology, the podcast about viruses, the kind that make you sick.

0:10From Microbe TV, this is TWIV, This Week in Virology, episode 1371, recorded on October 30th, 2026. I'm Vincent Racaniello. You're listening to the podcast, All About Viruses. Joining me today from Austin, Texas, Rich Condit. Hi, everybody. We have here... I'm just... My app is slow here, but it's okay. 69 degrees and rain. And that's awesome. Really good. Here it's 20C, which is 68, so about the same as you. And it's sunny. There are no clouds, but they have windy here on the, apparently it's windy today here in Chelsea. Also joining us from Western, Massachusetts, Alan Dove. Good to be here.

1:06And here in Western, Mass, it's 17C, 63 Fahrenheit. And it is breezy. Wind out of the north at 22, gusting 32 miles per hour, according to the Weather Service website. And I'd say that's about right. It's blowing leaves all over the place. well this is our penultimate day in october here folks we didn't come in costume sorry oh oh you know oh oh what missed opportunity man we should have done perfect yeah well this will be sunday released so it's kind of late i guess yeah but the spirit is still there i don't even have any anything reminiscent of halloween in this i have an orange an orange that's the color of halloween Yeah.

1:52And it's in an orange bowl. But sorry about that. I have a black cat on my desk. Oh, that's perfect. There you go. Perfect. I would say the month went quickly. But in fact, time, if you're at sea level here, it goes pretty much the same, right? But it felt to me like it zipped along. And before you know it, we'll be back in July, which will make me very happy. Well, we're up at the top of the gel. Is there at the top of the gel? Every interval is a smaller and smaller percentage of previous similar intervals. So it seems that it's all compressed. It's going faster. If you enjoy these programs about science, it's what they are about.

2:38We discuss the literature mostly, and occasionally we have guests. We would love your support to support them. You can go to microbe.tv slash contribute. There's one word in the news today, vote for Americans. Next week is an important election. If you're displeased with the current state of affairs, here on TWIV, we're displeased with the state of public health and science. And if you're displeased with other things, vote. That's the one way you can change things. Now, I found an interesting poll in the New York Times this week. It's called Swinging Away from Trump, and it's carried out by Echelon Insights.

3:22And they polled people who had supported Trump in 2024 and now don't support him anymore. And they said, what are the big issues? And the big one, 42 % of them said it was the cost of living, which I believe that. And I've been saying that for a while. But way at the bottom, the last category, 4 % are worried about healthcare. Folks, if you're not healthy, you're not going to be able to have a low cost of living. And, okay, so that's disturbing that people don't seem that health care is an issue. So why is it an issue? Because it's being trashed. Science research is being trashed. The CDC is being trashed.

4:02Our effort to track infectious diseases is being impeded. We have a measles outbreak, which there shouldn't be. And I could go on and on and on. That's great. It's not great, but that's the story. But then two categories. Well, the next category above it is immigration. Only 5 % of people are worried about the immigration. I don't know what that means. I'm not worried about immigration either. I think people should come here. But maybe they're worried about ICE and all that, but they're not. But the one that really bugs me next to science is democracy. Only 6 % of the people are worried about the democracy.

4:40Well, okay. So my reading of this is that the question that they asked is the biggest issue. for these voters. It's not that people aren't worried about the other things. What is your, pick your one biggest issue. And, you know, if you're on Medicare or you're gainfully employed and have health insurance, and maybe healthcare is not a big deal for you, you're healthy right now. But if you're, you know, or maybe healthcare, you're thinking long-term, you're thinking, yeah, I'm worried that Medicare is going to get cut, that my doctor is not going to be available. And definitely here on TWIV we're worried about science and public health.

5:24Democracy, yeah, that's foundational. But if people are three months behind on rent and about to get evicted, the biggest issue facing them is the cost of living. I guess. Yeah. But look, the reason you pay rent is because you're in a democracy. But that's a secondary problem for somebody who is about to be out in the cold. I got it. I understand. And there are a lot of people who are about to be out in the cold. There are a lot of people really struggling. That's too bad. Yeah, I just – you're right. That's the correct analysis. But when you look at it without thinking much, it really bothers you that people don't give a shit about the democracy, right?

6:05Well, okay. But they do. You're saying they give more of a shit about the cost of living. And that'll be bleeped in the episode, but more of a hoot about the democracy. I'm sure that that is a concern for a lot more people than listed as the biggest issue. And also, my own take on this is any reason to vote out the current stock of morons is a good reason. Oh, yes. If it's a cost of living. But these numbers add up to 100. I think so, yeah. Maybe. Yeah, about so. Well, yeah, whatever reason, just vote. And, you know, I hope next time we record, we're all content. I really hope so. Because I don't see how you could be happy with the current situation.

6:54Well, I don't think we'll be content next time we're on TWIV, because it will have been just after the election. Nothing will have changed. That's true. But at least there will be a future change. Hopefully things will be headed in a better direction. Well, of course, they may not let people see. You know, who knows what they're going to do. Crazy stuff. Crazy stuff. The founding people of this nation would not have anticipated this, right? Well, they tried. Yeah, I mean. They tried. But there was, I think, a fundamental understanding that, you know, people would be reasonably well behaved. No, but they did try to protect against, you know, somebody coming in and trying to be king.

7:41Yeah. And the, well, I mean, historically there were actually folks who wanted George Washington to continue as president and essentially be king. But all the flaws aside, the Constitution was structured to try to provide safeguards against a demagogue taking over. what they didn't contemplate was that an entire political party would go along with it. That's true. Founding fathers didn't have a two-party system. And they predicated a lot of this on, well, you'd have all these people in Congress who would stop a president from abusing his powers. Right. Or landed, educated individuals. Yes. Okay?

8:25Thoughtful. Well-read. And many of them owned a lot of people. Honest and trustworthy. Because that's a problem nowadays. A lot of people are not honest and not trustworthy. Yeah. What always amazes me is that a lot of the decision-making that we have is based on the assumption that the people in the group that you're negotiating with or whatever, making decisions, are rational individuals. okay uh who are not necessarily who are gonna you know try and see your part of it and blah blah blah no none of that's applies i really enjoy when rational people get together and have a great conversation and figure there's nothing like it i have never experienced the amount of irrationality as in the past what 10 years or whatever well i will uh insert my plug for uh public television again.

9:24The PBS NewsHour is amazing. The way they get on people of diverse opinions who actually have a discussion, all right, and give you both sides of the issue. It does tilt a little left, but my bias is that if you're very well informed about what's going on, you're likely to tilt a little left. The reason a lot of the news tilts a bit left is because they're trying to be reality-based. And unfortunately, the right in this country and probably some other places has over the past 40 or 50 years decided that they don't want to be reality-based. Hopefully that'll change. Yes, well, we'll see. You can be conservative and...

10:13And rational. Rational, yes. All right. So we talk about all kinds of things on Twitter because we're curious. I'm interested in understanding everything. I love viruses, and we mostly talk about that. But if you're asking why, we're not experts in politics, obviously. I don't know who is, but we are curious about it and like to figure out what's going on. And so that's why we talk. Anyway, we have some science for you. We have two. Well, the first one is a preliminary report. It's quite interesting that. So virological.org is a website run by Andrew Rambeau, a genomics type person, computational biologist.

11:04Eugene Koonin hates that word, computational biologist. I forgot what he prefers. Use computers to analyze nucleic acid sequences. Anyway, this is a preliminary report that's posted there. It's kind of like a preprint. It's going to get reviewed. And I just stumbled on it this week when I searched for, well, I was recording Rasmus and Retorts with Angie, and we were talking about this outbreak of H5N1 influenza virus in mink, and I found this paper. And it's really cool. Well, it's just a preprint, but we're going to talk about it. The title is Preliminary Report on H5N1, Highly Pathogenic Avian Influenza in Utah Mink, August 2026.

11:48And the authors, I'll just read them all because there aren't that many, Alvin Crespo-Bellito, Jennifer Havens, Thomas Peacock, Florence Debar, and Martha Nelson. And the team is from the NIH in Bethesda, the Perbright Institute in Woking, UK, Imperial College London, and CNRS Sorbonne Université in Paris. And I will say, so the paper is open access, but you cannot download the PDF because I guess there isn't one. Yeah, I've tried to do that. Yeah, I was like, where's the PDF link? I couldn't find any way to do it. You can read it on the site. You can make your own PDF, just print it. It's a preprint, so yeah.

12:27Anyway, let me give you a little background. This is an outbreak of avian H5N1 influenza virus on a mink farm in Utah. And so just to bring you up to speed, we haven't talked about this in a couple of days. In March 2024, avian influenza virus was detected in U.S. dairy cattle, which is a species that we didn't think would be infected by influenza viruses. And this was spillover from birds to cattle of an H5N1. The clade is 2.3.4.4B, and the genotype is B3.13. And this happened in Texas, and there was a human infection in March 2024, and a dairy worker infectious as well. But by May, most of the reported cases were outside of Texas.

13:22By the end of 2024, 917 U.S. dairy premises had cases. The virus had diversified into seven subclades. Transmission continued into 2025. In January 2025, a second clade was detected in cattle, 2.3.4.4P, genotype D1.1, first in Nevada, then in Arizona by the USDA testing milk. And by the time they found this D1, it's already widespread in North American wild birds and has since been a major source of poultry outbreaks and also human infections. In February 2025, Nevada reported its first H5N1 in an individual exposed to dairy cattle. So these are two distinct viruses that are circulating in cattle.

14:18So this paper describes an introduction of H5N1 into armed mink. So in cattle, dairy cattle, unlike beef cattle, they live a long time. Years, maybe even decades. And they continue carrying this virus for some time. It continues circulating in the herds. The cattle may be affected to some extent, but they're not keeling over or anything like that. And so this is very persistent in the U.S. dairy herd. Yeah, it affects milk production and milk quality. And, you know, this may be obvious, but the reason that we care is that human influenza infections originate way back in time and occasionally sporadically in birds.

15:17They spill over into humans. Not necessarily immediately transmissible, but they can become so they spill over into other animals as well and then spill over again into humans and this h5n1 is not a virus that ordinarily circulates in humans and does not actually circulate in humans now though it can infect humans uh occasionally and i want to hear comment on uh what it does under those circumstances but in birds this is can be highly pathogenic so i think you know from the human perspective and the potential of spillover that's scary All right? So we're watching any circulation in other animals concerned about whether this thing may change such that it can circulate in humans and be highly pathogenic.

16:06Now, there have been cases in humans, right, who've contacted dairy cattle and et cetera. What's – So it's interesting. So when humans get avian H5N1 from birds, it has a high fatality. Up to 50%. The cases associated with the B genotype from cows have been mild. The D genotype has not been. That's been more severe. And, of course, the worry is that because of the high severity in spillovers, we're worried that if it became pandemic, it would kill a lot of people. Although you shouldn't assume that it's going to maintain its pathogenicity, right? Right. You don't want a pandemic virus, okay? Right.

16:49I agree with that. But it may not be as bad as everyone thinks. And the D genotype that you said was more lethal in humans than the B genotype, where do we find that? So that was also first found in Nevada, then Arizona. In cattle? In cattle, yes. The second spillover, yeah. Right. So what's going on here, we've talked about this in the past. I'll just really quickly recap it. the longer the virus spends in mammals, the better the chances we think that it will be able to adapt to humans and establish human-to-human spread. So if you keep having it in cattle and these sporadic spillovers into human dairy workers, eventually the concern is that this is going to catch.

17:38The virus adapts to mammals to use a receptor that's more common in the upper lung as opposed to lower lung in us. In birds, it's a gastrointestinal virus, right? In birds, yes. In birds. So in humans, it's got to adapt to our lungs. Presumably in cattle, it's doing something to adapt to the udder. This is not the kind of experiment you want to run. And this idea that, you know, birds tip animals to humans causing a pandemic, That's not just fantasy. That happens. There are well-documented cases of this. Yeah. By the way, I just want to clarify, dairy cows typically live for four to six. Cows can live 15 to 20 years, but the dairy cows, their milk production stops four to six years, and then they're sold for beef.

18:32Right. Right. Beef cattle live shorter lives. Right. Was my point. These dairy cattle, they're eventually sold for, they're not great beef, but they're sold for beef when they can't produce milk anymore. Anyway, so the more animals that are infected with H5N1, the more of a problem it's going to be, right? You have more contact with people, more opportunities for the virus to be co-infecting cells with different influenza viruses and reassorting and so forth. So this is not good. In fact, in the last, I don't know, eight years, the H5N1 has infected more and more mammals of diverse kinds, you know, sea lions and hear cows and as we'll see, minks.

19:16So this is not good. Now, so back to the paper.

19:24Previously, there have been infections of captive mink in two European countries. Spain in 2022, Finland in 2023, wild mink in North America have been infected with clade 2.3.4.4b genotype A3, B1.2, and D1.1, but wild mink. And in all these cases, wild birds are thought to be the source of the mink infections. All right. Now, why we care about mink. So mink and pigs, we care about both of them with respect to influenza viruses because they have a lot of human-like sialic acid receptors, alpha-2 ,6-linked sialic acids in the upper tract like we do. And so viruses that infect them can become adapted to them, and they have a greater likelihood of infecting us.

20:18Now, mink are also highly susceptible to influenza viruses. We often isolate influenza viruses from mink, and they often get infected by the workers. And so the mink could be a vessel for reassortment between human and avian strains. And to recognize the importance of this, when H5N1 was found in a mink farm in Spain, they culled all the animals. They recognized the danger of having this. And if you remember, back in the beginning of SARS-CoV-2, there were infection of mink in the Netherlands, and they discontinued all the mink production in that country. Right. They discontinued the industry.

21:03The industry shut down. Yeah. It did. There were now European regulation of fur farms is a little different also because there's been vocal opposition against them. um you know people don't like this concept and that has gained more political traction in europe than it has the u.s so a country shutting down mink production probably had some other momentum behind it as well yeah i looked up uh what the market is for uh american uh raised mink and um There is no U.S. market. 80 % of the market is in China. Yep. Wow. Wow. I didn't know that. Yeah. Interesting. So the U.S. doesn't buy its own mink?

21:52Nope. Nobody cares anymore. Or they actively un-care. Yes. There's a lot of angst among people who would wear a fur coat that somebody is going to throw paint at them. Um, yeah. I know somebody who inherited a fur coat from a grandparent, um, and, uh, it's a beautiful coat. Um, but you know, do you want to wear it? Yeah. I, I don't like this idea of raising animals and then slaughtering them for their coats. I don't like that at all. There's an argument that if it's, if it's an antique, the damage is already done. So that's okay. Sure, sure. But the person, you know, the PETA activist walking down the street with the spray paint is probably not going to appreciate that nuance.

22:42The other thing is mink are mustelids, and so are ferrets. And remember, ferrets are models for influenza virus in a laboratory. So they're uniquely—they're good models for infection. So, okay, so August 17, 2026, they detected high pathogenicity influenza A virus, H5N1, in captive mink in Salt Lake County, Utah, by the USDA Animal Plant Health Inspection Services. These samples were collected from mink on August 7th. And as of September 29th, the outbreak is reportedly ongoing, although there are no samples after those first initial samples. Now, similar virus outbreaks have been found in dairy cattle in three other counties in northern Utah in 2026, but none in Salt Lake County where the mink outbreak has occurred.

23:42There's a nice map because you can get this paper. It's online. And they have a nice map of the U.S. with nice icons of cows and mink also. Okay. So they have 10 whole genome sequences of the H5N1 viruses in Utah mink. and they all are part of the B3.13 genotype that is circulating in cattle, as I just told you, in the U.S. They built a phylogenetic tree to look at the relationships and it's quite clear that these Utah mink viruses are within the 2026 B3.13 cattle claim, which includes all the strains collected in 2026 from dairy cattle in Idaho, Texas, and Utah. Now, there are apparently three interstate movement requirements for H5N1 testing and lactating dairy cattle.

24:40There are requirements, yet still the virus continues to move in cattle between the mountain region, Idaho and Utah, and the Southern Plains of Texas. So I guess the requirements are not being Maybe not universally enforced or maybe the testing is imperfect. The USDA is not terribly interested in H5N1 in cattle or mink. To put it mildly. I would say they are devoutly uninterested. Yes. So Angie Rasmussen has written, neither the state nor the USDA ordered the farmer to cull or monitored farm workers who may have been exposed. The USDA informed the state's head veterinarian there's no mechanism for authorizing vaccination or for compensating the producer for mink losses.

25:35Alleged fur industry pressure has discouraged any kind of regulation or intervention. and we don't really know what's going on. No one is surveying the cattle or the mink in this case, which is just a side note, folks, but it's not really that good. So then going back to the genome sequences, you can look at the genetic diversity and ask how long have these mink viruses been circulating, and it looks like they've been circulating undetected in mink for several weeks. the estimated time to the most common recent ancestor, in other words, the original virus that went into mink, is July 4th, 2026.

26:21And these Utah viruses form what we call a cluster, which means a single viral introduction, and then every virus diversified from that one. I love what you can get from sequences. Yeah, it's amazing. Yeah. Now, you can look at the sequence, obviously. When avian influenza viruses move into mammals, certain amino acid changes are selected for that improve replication in mammal hosts. And these Utah mink viruses, well, already have, sorry, the dairy cattle viruses, the B3.13 lineage, have a substitution in the PB2 protein, which is part of the RNA polymerase. It's M631L. That's known to increase replication in mammals, and that's been present in the cattle.

27:15The cattle strain also has neuraminidase mutations that may have been suggested to play a role in previous mint outbreaks. One change, a PB1K388R change was present in all 10 Utah mink viruses. And this has not been seen often in wild birds. It has been seen in the mink in Spain that were infected in October 2022. 2022. And so this may have been selected in some animal somewhere. We just don't know. I mean, we don't know anything about what K388R does, but it's emerged several times in mammals, so we need to figure out what it's doing. Okay, so that's the adaptation story. The most closely related ancestors of these Utah mink viruses are Texas cattle strains sampled in May of 20, 2026, but there's a three-month gap between that and detection in mink.

28:16And so we don't know how the virus has got. It doesn't necessarily mean it went from Texas to Utah. We could have gone somewhere in between. Do we have any idea? Oh yeah. If you look at the map and see where these Texas cattle are, they're up in the panhandle. Yeah. Because Texas, I'm, I'm looking at distances here. Yeah. And there's still quite a distance between there and the mink outbreak, but Texas is a big place. Yeah. And so is Utah, and so are the other states like New Mexico and Arizona that are in between them. I mean, if you're listening to this on audio instead of watching it on video or not looking at the map, or if you're not from the U.S.

29:00and you don't appreciate the sizes of these places, you can drive for days to get from one of these to the other. So it's possible that birds, right, wild or domestic birds, could be moving the virus from cattle to mink. We don't know. Farmed mink are also often fed poultry products. So maybe they were fed a contaminated product. Right, because they're carnivores. Right. In wild mink, birds are a source of HPAI, but this B.3.13 genotype doesn't transmit well in peridomestic birds like robins and grackles after spillover from cattle. And there's no evidence of wild birds seeding B.3.13 outbreaks in livestock after the introduction into cattle.

29:49I don't imagine there's a lot of human traffic between dairy farms and mink farms. I guess not. I think about these situations where I've visited, I guess some places in the U.S., but I'm thinking mostly of England, where you visit a farm sort of thing and you have to walk through a tray of disinfectant so that you don't track stuff out in your shoes. Well, there could actually be people moving between these places. Suppliers of one kind or another? Workers. Workers? I mean, amid this big push to deport everybody, one of the impacts of this is that food has gotten more expensive because the people who actually handle and process the food are often not documented in the U.S.

30:48and they are precarious workers who are moving from one job to another to send some money back home. It is entirely possible that somebody was working a gig at a Texas dairy farm and then moved on to do something at a Utah mink farm. I don't know. So the figure four in this preprint is very nice. It's a diagram of the transmissions that we know about, starting with wild aquatic birds. This genotype has gone into Spain, farmed mink into Finland, mink and raccoon dogs and fox farms. And then in the U.S., the B313 genotype went into cattle in Texas in 2024. And from there, it went into raccoons and chickens and humans and birds and cats.

31:37And then the Texas cattle infected Idaho cattle. The Idaho cattle infected Texas cattle again. And then the Texas cattle seems to be an ancestor of the Utah outbreak. And from the Texas 2026 to the Utah 2026, they have an arrow and it says, question mark, Utah cattle, Texas chicken, Idaho chicken, other host. We just don't know. Yeah. And a lot of the problem here is that we're not monitoring most of these. You know, we pay minimal attention to the cattle and we're not paying a lot of attention to the chickens unless they're dying. and, yeah, could have gone anyway.

32:19So also it doesn't look like the outbreak is frozen food. Some B313 outbreaks in cats appear to have been caused by frozen pet food. This was an interesting side note, yeah. So the way they can tell is you look at the genome change over time and you can plot it as a line. and if there was frozen food involved, frozen food will have been stored and you'll find a dot that's off the line because it's lost in time. It's a past strain that showed up again and what happened in the cat food is there was frozen meat that was then processed into cat food and then cats got this virus that had been frozen for some time.

33:08There's a paragraph called B.313 continues to migrate between Idaho, Texas, and Utah cattle. So Texas was the original epicenter. California then emerged as a national hotspot in the fall of 2024. Virus appears to have been eliminated in California. Then Idaho became the next hotspot in U.S. dairy cattle with 65 outbreaks in 2026. and phylogenetic analysis suggests there have been at least two B3.13 introductions into Texas cattle from Idaho during 2026 and two from Idaho to Utah cattle. But there's a lot of missing data. So there's a lot of, apparently, a lot of potential connections between Idaho and Utah.

33:59I'm sorry, Texas and Utah or Idaho in the cattle trade, right? Yeah. Yeah. H5 has also been found in dairy cattle in Kansas and Washington, but we don't have sequences. And so how they relate to the viruses elsewhere remains unclear. And it's also entirely possible that there are dairy operations in Utah that may even be close to this mink farm that we just haven't identified as having virus. That's kind of where I was going with that. Yeah. I mean, if this virus is moving back and forth in cattle, that's a way to get it closer to the mink from Texas. And we just may not, there may be missing links.

34:47and so they end the paper with some outstanding questions which i like so the first one is how did b.3.13 spread from cows to mink and they say in europe birds wild birds like gulls are the most likely source of the outbreaks in spain and finland and mink the genetics tells us that and also gulls are attracted to food waste in mink barns we don't know how the virus got from Texas cattle to Utah mink. Shared workers, vehicles, or equipment are thought to spread among cattle farms, but the mink get food from a wide variety of sources that come long distances, could be poultry or even cattle products from another state.

35:34Right. So they say our inability to pinpoint the source of the Utah outbreak points to large surveillance gaps for highly pathogenic avian influenza in U.S. livestock. I can't help but imagine whether in another administration we wouldn't have these surveillance gaps. Well, this is this is a complicated problem when you start. I don't know. I'm just saying. Yeah. Yeah. No, I don't think we would. The USDA has a split personality. Its job is to promote American agriculture and also make dietary recommendations for Americans. So there's some conflict between those two. But on the promote American agriculture side, I mean, agriculture everywhere and certainly here works at razor thin profit margins.

36:28So as soon as you start saying, well, why don't we change this one small thing in agriculture? All right, you got to multiply it by a billion. I mean, because it's just the scale of things is so huge. You want to change something in dairy farming, how much do you want your milk to cost? And if you start testing more, well, the test costs a little bit of money, but what's really going to cost is any kind of intervention that's going to have to change industry practice. Or in this situation with the mink farm, if you're going to take the European approach and cull all the mink, I think by law the government is going to have to compensate the farmer for that.

37:08And that's going to cost money and it's not going to be very popular. So a lot of the inertia on testing comes from a broad political base, and I don't think that we would necessarily have more testing in a different administration. There are many things that we would do differently and better in a different administration, but I don't think that's one of them. By the way, people may be thinking, well, when there's an outbreak of H5 or HPAI on a chicken farm, you have to cull all the chickens. And the reason you do that is otherwise you can't export any chickens. We have the biggest export of chickens in the world, and that's very precious, and they don't want to mess with that.

37:55So we've done 200 million chickens this year on farms culling. But there's no rule for mink because, I don't know, I guess you can export a pelt from a H5 mink farm. Yeah. Doesn't matter. Okay, so back to another question. Will the virus spread to additional mink farms? There's only one farm in Utah that's affected so far. They don't know. There are other farms, right? And they say, in contrast to pigs and cows, mink are not routinely transported between farms. Yet, in 2020, SARS-CoV-2 spread between six mink farms in Utah. So how does that happen if the mink are not? People. Maybe wild animals.

38:42People, wild animals. Sure. I mean, SARS-CoV-2 is so promiscuous, it could have infected anything as an intermediate. They say that local free-roaming cats have been infected by mink, so they could spread infection as well. Mink infected with SARS-CoV-2 were not culled, and there are no plans to cull HPAI-infected mink in Utah. How about vaccinating the mink? There is a Zoetis H5 vaccine, which is licensed for use in animals or reimbursement for depopulated animals, requires the USDA to establish mink-specific regulatory authority and dedicated programs for HPAI response in mink. And as Alan said, that costs money.

39:26And there are no efforts underway, the authors say, as far as we know, to test mink on surrounding farms or wildlife in the area. Previously, this same group reported spillover of SARS-CoV-2 Delta from farmed mink to wild, white-tailed deer in the same area. And they give a link for that. This is all very interesting, isn't it? Yeah. Another question, is the virus already adapted to mink or will it continue to adapt to the new host? And they say, well, we don't know because we have sequences from the beginning of the outbreak, so we don't know what's going on. Another question, too early to tell.

40:07How much cryptic transmission occurs in cattle? And they say almost three years into the outbreak in the U.S. cattle. The virus appears to have been eliminated in most states, including California, which they say is a major achievement. However, persistence in cattle in Idaho, Texas, and Utah provides opportunities for spillover to new species like the mink. They say despite active surveillance, large gaps in dairy cattle, sampling gaps, make it difficult to track what's going on. What other U.S. mink populations are at risk for B3.13? There are two states where B3.13 continues to circulate, and dairy cattle, that's Utah and Idaho.

40:53And they also happen to be two of the country's largest mink producers. I learned something on TWIV. Yeah, weird. I didn't know that. Texas does not have commercial mink farms. They tend to be in the cooler climates. And, you know, we have never found B13 in Oregon or Wisconsin. There are other H5 clades circulating there, and they've been detected on dairy farms like the D1 genotype. We don't understand why there's no spillover of H5N1 from wild birds to mink in North America, especially since it happened in Spain. That we know of. that we know of. They say there are gaps in our understanding of HPAI ecology in North America, especially in gulls.

41:42I think we ought to be doing a lot more sampling and research in this area because it's not only fascinating, but it's important. So that's the story, folks. In case you were wondering, it's not something to say, it's not important, which the USDA is seemingly saying. I think this is important and we need to be careful. And if you want things to change, you know what to do next week, Americans. Okie dokie. Next paper, Cell Reports. This is more of our normal type of—this is a refereed published paper in Cell Reports. Species-specific gene programs define divergent antiviral responses in Marburg virus reservoir bats and humans.

42:31And the co-first authors are André Philippe Pastor and Shruti Shursathe. Senior author is Gustavo Palacios. The team is from Mount Sinai School of Medicine in New York. The CDC in Atlanta. I'm encouraged to see that they employ at least one researcher. The NIH in Fort Detrick, Global Health Emerging Pathogens Institute in New York, and University of Georgia, Athens. It includes our buddy Jens Kuhn. Yes. Jens Kuhn, who's been on TWIV, and also Gustavo Palacios has been on TWIV as well. Gustavo has been working on Andes virus, so I'm trying to get him on to TWIV to talk about what's happening with that.

43:14And Adolfo Garcia Sastre is also on TWIV. He's also been on TWIV, yes. And Jonathan Towner, he's a CDC guy. We're eventually going to read all the authors. He has not been on TWIV, but I want to get him on TWIV because he's a guy who goes to Africa and looks for Ebola viruses and bats in caves. Cool. He does that. And I met him at a bat meeting a couple of years ago. He said he'd be happy to come on and talk about it. All right. So this is another bat paper. We've done a couple of bat papers recently. And too bad that Angela isn't here. She likes bats. But here's the bottom line from this paper.

43:54It's something that Angela said. A bat is not a bat, which means what you find with one kind of bat doesn't mean all the other bats are the same. If you've seen one bat, you've seen one bat. You've seen one bat. So bats are order charoptera, right? It's got two suborders, yin-tero-charoptera and yang-charoptera. Oh, how clever, yin and yang. It's the second most diverse group of mammals after rodents. and they say here they have evolved to accommodate increased metabolic rates needed to support flight and hibernation. And at the same time, they seem to host a lot of viruses, a broader array of high-consequence viruses, some of which are associated with zoonotic transmission to humans and other mammals.

44:44And they say, you know, many of these virus infections in bats are subclinical or paucy-symptomatic. That's a nice word, paucy-symptomatic. And we think it's because bats have a different response to an infection than a human does. All right. For example, one difference in bats is the contracted type 1 interferon locus. This is in Ying, Ying, Ptero, Chiropter, and Black Flying Foxes. And this contraction coincides with constitutive expression of interferon alpha in those bats. And they also have a broader distribution of type 3 interferon receptors, basal expression of another transcription factor that's important for interferon.

45:36And then a different bat, the Ying pterochiropteran Egyptian rosette bat, their genomes have an expansion of functionally active interferon omega genes, but baseline expression of type 1 interferons is limited. So there are differences among these different species, as Angela would remind us. In fact, some don't even have interferon alpha genes, which, of course, humans do. So they say that findings from examining bat immune systems are often extrapolated from one species to the entire genus or the entire family. And they say this is not correct. They give a whole list of examples. For example, Marburg virus subclinically infects Egyptian rosette bats.

46:28It's cleared within two weeks after exposure. But humans, of course, do very badly with Marburg virus infection. We have innate responses very early on that cause a lot of inflammation and cytokine release and tissue damage, vascular leakage, et cetera, et cetera. And, you know, in studies that have examined a single species to different filoviruses, they have yielded contradictory results. For example, Angolan free-tailed bats only replicate Ebola virus, but the Ebola virus, but not Reston or Thai Forest or Marburg virus. Jamaican fruit bats exposed to Ebola or Marburg only replicate Ebola in the absence of clinical signs.

47:20Egyptian rosettes exposed to Marburg or Raven virus became viremic, but exposure to five distinct other Ebolas did not result in systemic replication. So they say, based on these results, we suggest that any generalization is inappropriate and each virus host interaction must be distinctly studied. So to do this, that's what they're going to do in this paper. They're going to compare infection of one virus in its natural reservoir and its accidentally infected host. And so that is the Egyptian rosette. They have dermal fibroblasts from Egyptian rosette bats and humans. And these are, by the way, these are also called Egyptian fruit bats.

48:06I don't know if we've mentioned them on TWIV before, but they're fruit bats. Right. They're cute. I like the name Rosette. It's a nice name. Okay, so now they take these cells that are growing in culture, and they're going to sequence the RNA. So you can see what's turned on when they're doing things to the cells, right? Transcriptomic data. This is a data-heavy paper, folks. It's got lots of charts and tables. And it is open access. Yes, so you can go look at it. So they're going to treat these cells for four hours with poly-IC, which is a double-stranded RNA, synthetic double-stranded RNA that turns on innate responses.

48:49And that poly-IC is delivered to cells in a facilitator called lipofectamine that helps poly-IC get into the cells. And the control is just lipofectamine alone without the poly-IC. And then they're going to do this in the human and the bat cells, and they're going to sequence the RNAs, and then they're going to look at differential gene expressions, okay, between the Egyptian rosettes and the human fibroblasts. And so this gives them four kinds or four sets of genes that they find after doing this. All right. First, so they're looking at differentially expressed genes, right? Things that are turned on or off.

49:36The first set, 398 genes before poly IC stimulation and 164 before interferon A stimulation, have lower expression in human fibroblasts at baseline levels compared to Egyptian rosette fibroblasts. And these are called, wow, human constitutive low, HCL. Okay, that's number one class. Number two is a set called bat constitutive low. They have low expression at baseline compared to humans. That's number two. Then number three, they have a set of genes after poly-eye stimulation that go higher in the bats compared to humans. So that's bat-induced high. Just keeping track of this. And number four, a set of genes that after interferon stimulation, they have higher expression in human fibroblasts compared to Egyptian rosettes.

50:36So that's human-induced high. Okay, so BCL, bat-constitutively low, low in bat cells at baseline, higher in human cells. HCL, humans-constitutively low. These are low in human cells at baseline, higher in bat cells. Then we have BIH, bat-induced high, strongly induced in bat cells, not in human cells. and HIH, human-induced high, strongly induced in human cells, not in bat cells. Got it? So they're looking at what are the differences between humans and bats, gene expression, normally— Baseline. And then when induced with this poly-IC stimulation that simulates infection. Okay. So here, I'm going to summarize the results.

51:29Because, you know, when you read this paper, they have all these neat gene names that go on for many, many lines. It's very difficult to come to your thought. If you were an expert in this, those would all mean something. Yeah. Okay? But to me, there's just an assortment of gene names. And I look for the summary, you know, that they say, you know, that these are involved in, you know, inflammation. These are involved in antiviral state, et cetera. So first of all, bat cells induce antiviral effectors. They induce RNAs that encode for proteins that just have antiviral properties, like zinc-binding protein 1, ZBP1, and a bunch of others.

52:14These are known to have antiviral properties. The inflammatory genes, like chemokines and IL-6, classic pro-inflammatory cytokine, they're restrained in bats. Okay. In contrast, human cells induce a broad inflammatory and cytokine program. So lots of chemokines and cytokines along with toll-like receptors and RIGI gene products, proteins that are going to sense viral RNA and also genes tied to necroptosis and apoptosis cell death. Okay. So human cells are like just blasting. Yeah, the way I interpret it is bats have a narrow kind of tailored response. Human cells freak out. Yeah. I was going to use the word focused in the bats.

53:10That's what I was thinking. So we had the same idea. They say rosettes. These are rosette bats, right? mount a robust yet restrained response with effective antiviral proteins and limited inflammation. Human cells respond with indiscriminate inflammatory amplification, which the authors hypothesize contributes to cytokine-driven pathology in Marburg, for example. Burn it all down. Yeah. Indiscriminate translates to freaks out. Yes. Freaks out. So that was transcriptomics, all right? They also do proteomics. They look at the proteins to make sure that this is true for the proteins, right? Because if it's not, that wouldn't be good.

54:01Pretty much agrees with the transcriptomics, okay? All right, so these are data that they generated by having cells in culture and adding these things and doing the RNA sequencing. They also look at other data sets published by other people to see if the signatures hold up. They have human tissues and rosette tissues. They have spleens from Marburg virus-infected rosettes. What they see in these other data sets are consistent with what they have shown in their cell cultures. Now, there's a whole section on interferon epsilon, and this is worth a little bit of introspection. So, people have used rosette, respiratory, and intestinal organoids to look at similar question.

55:01And these organoids have elevated constitutive levels of innate immune effectors like type 1 interferon epsilon and also interferon-stimulated genes. So epsilon type 3 is a type 3 interferon, right? And mRNA is highly expressed in Egyptian rosettes, small intestinal organoids, and also nasal, bronchial, air, and liquid interface cells. This constitutive expression of epsilon interferon is thought to be a contributor to constitutive antiviral immunity in bats. In human organoids, they mostly make pro-inflammatory cytokines and chemokines, as we have already said.

55:54And so they concluded in this previous study that interferon epsilon production drives bat immune resilience. Okay, so this type, this epsilon interferon is very interesting because it's not induced by known pattern recognition pathways like the tolic receptors and so forth. It's mostly constitutively expressed in epithelial cells of reproductive tracts, both mice and in humans. And its expression is hormonally regulated, particularly by estrogen and progesterone. So it seems to play also a role in bat immunity as they're finding. And they say our findings largely corroborate the understanding of human epsilon.

56:46It has tissue-specific expression. It's not inducible by viruses. Egyptian rosette interferon epsilon is not expressed in most immune tissues. Its level is higher in brain, ovaries, and liver. So it doesn't change after infection. So that's the same as in humans. So that's the story. Those are the data. Now, just a few things here to note. This is mostly done with dermal fibroblasts, right? So that may not represent the right cell. I don't know. Even though they validated it with other systems, it's still, it's really correlational. Fibroblasts are basically one of the easiest cells to culture.

57:34They're a part of connective tissue. They're important in wound healing and that kind of stuff. You know, they're kind of the blue-collar workers of tissue organization. They, you know, hold things together and stuff, but they're not specialized to deal with infections or immunity or anything like that. Yeah, I mean, the disease is driven by immune and endothelial responses, right? Right. fibroblasts so and fibroblasts are neither at the immune front line or at the interfaces of you know they're not the the top epithelial layer yeah so i mean and i mean the minute i typically when i see a paper like this and they're gonna uh uh culture cells and extrapolate to uh animals from the cultured cells i'm immediately suspicious okay um they also i spent some time because at some point or another they call these primary cells which is not true okay because formally the definition of primary cells is that they are the cells that grow out before you ever subculture when you stick a disaggregated tissue into a dish and that will be multiple cell types it only takes a couple of passages for whatever the media is selecting for to grow out a more specific cell type.

59:08And typically, you know, you're running the mill media for many tissues. What grows out are fibroblasts. And I looked these up in the ATCC and that kind of stuff. And they talk about how these cells are at like passage 14 or something like that. So they've been subcultured a few times. They've selected for pretty much a pure fibroblast culture. But to me, what's important about this is that when they compare their results to whatever they know from either bats or humans, they're pretty similar. Yeah. Okay? So, in my mind, what they're doing, since the human experiments and the bat experiments are difficult to impossible to do, is justifying this as a system where you can get a first glance at what's going on.

59:56And as we said at the top of the show, if you've seen one bat, you've just seen one bat. Now this gives you an easy way to go get fibroblasts from a bunch of other bats and compare them and see if you get the same thing. And with this as background, I won't just, when I look at it, just discard it as fibroblasts. Okay, I'll say, oh, well, that's interesting. It's also interesting that this is cell reports resource. Right. I was interested in that. And basically, part of the motivation of this particular publication is to provide technical and experimental resources for other researchers. And to me, that's what this is.

1:00:37This is a resource. You can do this in fibroblasts, and, you know, the results probably mean something. Yeah. So the first, actually, most of what we've talked about so far is these experiments where they're just looking at cells in a dish, fibroblast cells, as Rich explained, and sticking on various artificial stimuli. That's not an infected bat. That's not an infected human. But then they go and take the critical step of validating that to the extent they can against data that we have from bats and humans infected with Marburg virus and getting similar patterns. and then they can say, okay, these things correlate.

1:01:25So you can do your experiments in this much more tractable system where you don't need bats as your model or infected humans in an outbreak zone and you don't have to gown up in bubble suits in your P4 lab to work with live Marburg virus. You can actually do a lot of science on these cells and then spot check against reality. Yeah, I think this is a... Good starting list. Now, you have a list of genes that we know differ in human versus bat fibroblasts, right? And we don't know if they explain the difference, say, in Marburg infection of bats versus humans. But now you could take some of these genes and do the experiments that might address.

1:02:14You can't do it in humans, but you could do it in bats, for example. And that's why this is a cell reports resource, because now people can take these lists of genes and the transcriptomics and the proteomics and go further and do more experiments. So this is a paper that has kind of a call to action. Try this at home. Go do your own bat cells. I mean, these things need to be done. They're important questions. So that's the story there. Okay. Let's do some email. Rich, can you take the first one since it references you? Okay. Let me scan down here. I was putting in a new title. Try this at home.

1:02:59Try this at home. Okay. Jerry writes, Vincent et al. It's a pleasant fall evening, but it's really a stretch to call it autumn in Northern California. Rich mentioned Richard Feynman, his father, and bird names. There are important issues with birds and names. This guy, I've read this email. He knows a thing or two. First, and what Richard's father is pointing out, does saying that a bird is a teal or a rind tell you anything about the animal? No. It tells you something about the humans. If you want to understand that bird, you have to study the behaviors and ecosystems. And in fact, I think that's what Feynman said in the book.

1:03:50It rings a bell, though it's been a long time since I've read that stuff, that his father, Feynman's father, in commenting on the same topic, says, doesn't tell you anything about the birds, it tells you about the people. Okay? Very interesting. Second, we travel around looking at birds and animals. There is an entire class of people who are listers. They only want to add new animals to their list. The most notorious are birders. The stories about them are truly horrifying. When asked if I'm a bird watcher, I will often say, no, but I really enjoy looking at them. Jerry. Very nice, Jerry. Thank you.

1:04:28So there is a video on YouTube about what Feynman said. What's the name of a bird? Good. And so basically he said his father taught him knowing the name of a bird in multiple languages reveals absolutely nothing whatever about the bird. Fine. But shouldn't we still name birds? Otherwise you'd call it number one, number four, right? Absolutely. And I went through this head thing when years ago I had to, and this has all changed now, Years ago, I had to tackle, in a general sense, the idea of the topic of taxonomy for fields of virology. Why do we do this? Why do we classify things? And the fact is that if you have a name for something, then there are properties associated with that name.

1:05:22And so if something else has the same name, you can assume it has the same properties. And that, you know, it helps, it aids in communication. but there is a lot of just sort of, you know, we love to have names for stuff, I guess. Look, we call viruses names, right? Maybe you have to. Yeah, exactly. Because the name gives you some information about the virus, right? Names are our cultured cells. They're our way of referring to things. So a name of a virus can refer to the disease, right? or poliomyelitis virus or influenza virus. But rotavirus does not. That's kind of the wheel-like appearance of the virus in electron microscopes.

1:06:12So it can mean different things. Coronavirus, right? That refers to its appearance. By coronaviruses, they're small and have RNA. Right. Right. The comment about birders being notorious listers. I don't know where it was I read this, but it was about bird collectors and that kind of stuff and about how they are such fanatics that, and I don't know if this is still the case, but back in the day, bird collectors would actually have collections of bird carcasses, all right? And this is a big deal. And people had big collections and that kind of stuff. There was a story I read about one of the most famous collectors.

1:07:03I think after he was gone, they realized that a lot of his collection, he had surreptitiously stolen from other collectors. The person who discovered this was going over his collection. She described herself as having attention surplus disorder. That allowed her to figure this out. So what is a lister? Someone who wants to make a list of things? Someone who checks off, you know, I've seen this bird, this bird, this bird. And to be clear, you know, this is not to describe all bird watchers. There are people who are more casual about it. It's like any hobby. And people who are fanatically dedicated to it, who organize their vacations and go on foreign trips to, you know, see the birds of other countries.

1:07:53hey the elderly couple in patagonia who went on a bird watch oh yeah they came back with the indies virus right they both are dead now right so i don't see i mostly see sparrows because there's so many of them they've just flitting around occasionally i'll see a blue bird occasionally a cardinal that's cool a red bird right one of the things that interests me is I think if you're really into this, it sort of expands your awareness of birds and you see a lot more than other people see. Yeah, I'm not looking for them. I mean, they're very interesting. I think what's cool is when you see an unusual bird, occasionally at night I can heal owls, right?

1:08:37That's pretty cool. We have a pair of great horned owls in our neighborhood that go back and forth in the night And you can hear them. I had to look up the call to figure out what kind of. I saw one of them once. Huge, huge owl up in the tree. And they just, you know, back and forth. Hoo, hoo, hoo, hoo. This is my tree. Yeah, well, this is my tree. You know, I'm sure that's what it is. Also, hawks are cool to see. Hawks are cool. In my old office at Columbia, sometimes red-tailed hawks would sit on the ledge. Yeah. Because they nest in the GW Bridge. and occasionally they would sit on the ledge because they would hunt for rats and stuff down below.

1:09:18And that's so cool when I would just see them sitting there. Man, because they're very striking looking with the curved beak and all that. So if you want to be really cool and you're out with your friends and you see what's obviously a hawk going by and somebody wants to know what it is, just tell them it's a red-tailed hawk because there's a 90 % chance you'll be right. Yes. Is that right? Even if you don't know any better. Right. I think plants are cool too. It's neat to see different kinds of plants, right? Especially if you're walking to trees. You don't see a lot of insects typically unless you dig in, you know.

1:09:51My wife is just great at this. We'll go out for walks, and my mind is all screwed up about, I don't know, politics or some triviality or something. And she'll say, oh, look at that flower. Isn't that pretty? And I would have just walked right by it. And so she draws my attention to what's beautiful right in my neighborhood. But, you know, most animals don't want to be seen by you. Right. Look at the birds. They're way up there. They don't care. Right. Anyway, Alan, can you take the next one? Sure. Terry writes, Hello, Vincent. My husband and I are both veterinarians, and we started listening to your podcast during COVID.

1:10:28We love listening to you and Daniel, and we are grateful there are people like you who inform the world using science. As veterinarians, we deal with people who don't want to vaccinate their pets. And we try as hard as we can to help them understand the importance of vaccines and which ones are needed. We live in Minnesota, so Lyme is an obvious discussion we have. I have been referring to the CDC's official health advisory on rabies daily, and that has helped me convince people of the importance and provides a link. I'm wondering what your take is on this from the CDC. and this is a CDC health alert network.

1:11:03Again, nice to see something still functioning at the CDC. Nationwide increase in reported human rabies exposures, rabies post-exposure prophylaxis administration. And this is, yeah. This is human. This is human, but they're coming from animals. Yeah. And people are apparently getting more exposures. from July through August 2026, CDC received 17 % more rabies-related inquiries than during the same period in 2025, including reports of mass exposure events, which is just involving more than one person. Mass suggests like hundreds, but could be two. But still, during this time frame, They had a bunch of state health departments call in.

1:11:52And, yeah, they talk then about correct administration of the rabies vaccine. Typical course of post-exposure prophylaxis can cost$11 ,000 to$14 ,000. Wow. Holy cow. Would it be covered by your insurance? I sure hope so. I hope so. Not everyone has. Why is that? Well, I guess because it's post-exposure, you have to do more. Because they would give immunoglobulin as well, I guess. Yeah, it's immunoglobulin plus the vaccine, I guess. Yeah. But still. They've got a whole special page that I'm looking at here on the actual protocol. Wound care, immunoglobulin, and the vaccine. And there are common horror stories about getting the vaccine in your belly and that kind of stuff.

1:12:44That was an older vaccine. The vaccine is much more tame in terms of its administration. I got it. Since we volunteered at the local animal shelter, they happened to have a rabies vaccine clinic. So, of course, we all was like, sure. And I would say it's a little more painful than a flu shot. nowhere near as bad as the COVID-19 mRNA vaccines, at least for me. The problem is that if you're a human and you get rabies, by the time you know it, you're dead. You die. You die. So there's no taking any chances here. So, yes, if you get bit by something, you should get a rabies vaccine. Yep, absolutely.

1:13:39Now, here on this page, which I think this page is pretty good at the CDC, it says, if the animal that bit you is not your pet, ask the owner for proof the animal is up to date on their rabies vaccination. So this email is originally about convincing pet owners to vaccinate. If your pet has rabies and bites someone and gives it to them, man, you are liable. And not just for the$11 ,000. You are on the hook for some serious money. So - I don't know why you don't want to vaccinate your pets, but you really need to. Also, if you have a dog, I certainly hope this is the case in all 50 states. In all the ones I've lived in, it's been the case.

1:14:22You must vaccinate your dog against rabies annually, and you have to have the tag that says so. And if you don't, and you don't have your dog license, your dog can be confiscated and put down. In fact, dog tags often have rabies vaccine on it to show that. I mean, they give a tag for cats too. And I guess if you had an outdoor cat, you probably ought to put the tag on it. But if you have indoor cats loafing around like we do, you can just file the tag. So your cats never go out? Well, one of them got out a couple of weeks ago and ran himself up a tree and we had to get him back down. It was his first time ever outdoors, and I don't think there will be a second time based on how traumatized he was by that.

1:15:07But they're also – they have their ID tags and they're chipped. So if they're found, it would be easy to document that they're rabies vaccinated. So the rabies vaccine for humans is an inactivated rabies virus. Yep. The rabies virus for pets is a pox virus vectored rabies glycoprotein. So I think they use canary pox frequently. Yeah. Cool. I wish they'd do that in humans just to be cool. Well, but the one for pets has to be, this may just be like a carnivore immunology thing for dogs and cats, but it has to be given either every year or every other year, I think. True. Whereas the one for humans is, I believe, you know, once you're done with a three-shot course, you're done.

1:16:04So I would not want an annual rabies vaccine. No. Yeah, my cat has to get annual rabies vaccine. And I'll tell you, for that poor cat, visiting a vet for us, too, is just not a good time. It's an unpleasant experience for everybody. Not a good time. You know, Ashi is just a wonderful being most of the time. But get him near a vet, and the whole world changes. It's terrible. Yeah. Poor guy. All right. Charles writes, Hello, Twivers. Great weather day in Chapel Hill, 20C with some puffy clouds. A great day for a walk in the woods. On my way to the woods, I was listening to TWIV 1369. Although, and I thought my email tagline was perfect for part of the discussion.

1:16:52Freedom from responsibility is not liberty, it is childhood. Thinking about people not taking responsibility for getting vaccinated and not having their children vaccinated sparked that line. While I was walking in the woods I hiked in today. If you're going to be a grammar Nazi, I know there's a common splice and I decided to leave it. The pushback has to do with the idea that no virus is going to wipe out the human race. Okay, none has for 300 ,000 years. How about the maybe impossible recombination of rabies and bovine ephemeral fever virus? Something as deadly as rabies recombining with something that spreads somewhat fast and that we may not be able to vaccinate against in time.

1:17:33Maybe I should listen to something else before hiking in the woods. So has there ever been an example of a virus wiping out a species? Oh, I'm sure. I'm sure, but we don't know about it, right? There must have been, right? Because there's so many years of species and viruses that it must have happened. But we don't know. But, so the problem, Charles, is that you're assuming that these properties would remain the same in the recombined virus, okay? High lethality and high transmissibility. You don't know that, right? So look, I cannot say a virus will never wipe out the human race. That's not how science works.

1:18:11But I can say I doubt it because lethality is not necessary. What's needed is transmission, right? That's the driving force for a virus. And so lethality is something that humans get afraid of for understandable reasons. But it is not what drives virus evolution. Matter of fact, killing your host is kind of a dumb idea, unless in the process you somehow boost transmission. Maybe a rotting corpse is a good source of transmission. Well, Ebola kills and it transmits very well because people prepare the bodies for burial, etc. But even the most lethal virus that we have seen, right, 1918 influenza, did not kill more than, what, a couple of percent of the human population, which is a lot.

1:19:04I understand a lot of people dying is not good. But there's always going to be someone resistant, right? There will be someone resistant. The virus will evolve to not kill hosts or at least not to kill them fast because, as Rich said, that's a bad move. Um, and, um, so I just, I, two comments came to mind for me reading this email. First of all, just replace the comma with a semicolon. You're good. Um, second, um, you know, I don't expect a virus to wipe out the human race. As Vincent said, we can't say it's impossible in science, but we are too outbred and diverse and somebody is going to be immune.

1:19:44But you don't need to go anywhere close to that extreme to make things really, really bad. COVID-19 case fatality rate was maybe 5%. I think much lower. Maybe a couple of percent. And it shut down the world for a couple of years. It was hugely disruptive and millions of people died. If you had something that was 10 % lethal, you wouldn't recognize humanity that came out the other side. All this would fall apart. So the global infection fatality rate for COVID was between 0.3 % and 0.6%. Okay. It still messed things up, right? It varied a lot country to country. It did. It did vary. There were some that were up 50%.

1:20:35And also with age, right? So if you're older. Yes. If you were over Medicare age, you had a much higher risk. All right. Rich, you're next. Rona Rice. Dear scientists, I listened to episode 1369. I have a question about a consequence of Florida proposing to remove its vaccination mandate. The PNAS paper you refer to plots that herd immunity of measles will be lost. My question is, given the consequence of the rise of measles cases, could there be a scenario that the new cases of rampant measles could develop a variant that will no longer be matched with the current vaccine? And even the vaccinated will potentially be in trouble.

1:21:24In curiosity, Rona. I think that's a really interesting question. My first reaction to that was probably not because the measles, and I don't understand this. Maybe you can explain this to me. It seems to be, even though it's an RNA virus with potentially a lot of drift, it seems to be pretty stable. The vaccine that was developed, well, I guess it's only now 40, 50, 60, 60 years ago, has remained quite effective the whole time. And there hasn't been any, there haven't been variants, vaccine escape variants that have arisen. So that's why my knee-jerk reaction is no. On the other hand, now you're proposing a scenario that we haven't seen before, where you have an outbreak of measles in a population that is largely vaccinated.

1:22:25I don't know how to think about that. I think we have seen a scenario that was a variant of that, which is before the vaccine came along. Um, you know, this virus had a lot of room to change and yet people would only get it once. True. So you get over the measles virus, you have antibodies against it for the rest of your life. If you, you know, survive, um, you may have sequelae that you deal with the rest of your life, but that was, that was the progress of the disease to immunity. And that was one of the indicators that a vaccine could work because people who'd had it were immune. So how come some RNA viruses I'll address specifically, you know, throw off a lot of variants that require, if you like, vaccine updates and stuff.

1:23:24I mean, flu is kind of a special case because of the segmented genome, the bird reservoir, okay, and other characteristics. I think you don't need a segmented genome to undergo antigenic variation. You just have to have a mutation, right? But I think your glycoproteins need to be able to accommodate the changes. Right. So it's a fitness thing. Do you remember we did a paper years ago where they looked at this in measles virus? And they mutated the glycoprotein up and down, and they're parts that can sustain changes and other parts that cannot. Kind of like those planes, right, coming back from battle, Alan?

1:24:01Yes. Yeah, yeah, yeah, yeah, yeah. So it's a fitness thing, okay? Of course. You can't mess with it. And, you know, as I recall, antigenic variation in flu, there's all kinds of spinach in the hemagglutin and surrounding the active site that you can tinker with, okay? It's fitness. It's all about fitness. Yeah, I think of this, this may not be a very helpful analogy, but if you've ever seen pictures of the sort of Einsteinian model of space-time where gravitational wells are in a cloth, you know, and Earth is 1G down in the cloth in this fold. And you can climb up the gravitational well and get to another planet and then go down its well.

1:24:48evolutionary adaptation is like that where depending on how deep your well is you may not be able to climb out of it to get to some other adaptive space or there might not be some other adaptive space that you could get to because you're constrained whereas something like SARS-CoV-2 is much shallower on the surface if you will and it can kind of move around with impunity Again, maybe not a helpful analogy, but that's how I visualize it. So the TWIV consensus on this is that given the history and what we know about measles, unlikely that we're going to get that kind of variance. Still not a good experiment to do.

1:25:31No, and a damn interesting question. Yes. You're thinking, Rona. Yes. Cool. Very cool. Well, the question is, have people made antibody-resistant rabies, measles virus, right? I do not know the answer to that. In the laboratory? Yeah, antibody escape mutants of measles. Don't know. Somebody out there must know, right? It's a lot. Yeah, I don't see any papers on it, but it could be. All right, we have one more. Alan, can you take that one? Sure. Aldo writes, Dear Twiff Team, I'm enjoying the program a lot. In the National Reference Institute in the Netherlands, I participate in the diagnosis of rabies.

1:26:17In the Netherlands, we do not have the classic rabies, but we have European bat-lissavirus in bats. But this virus has not caused a lot of infections in other mammals. Recently, we found, however, a cat positive for bat-lissavirus type 1 provides a link. Infections in other mammals were seen sporadically in other European countries. Many cats will catch sick bats, and one would expect more infections with European bat-lissa virus. I remembered a paper in which rabies virus was characterized by monoclonal antibody, and clear differences were shown between fox strains and raccoon strains. Even when the habitat overlapped, the strains in the different species were different.

1:26:58What I remember as an explanation was that foxes are extremely sensitive to rabies and die too soon from the raccoon virus. The fox virus was relatively low in virulence, which allows transmission after infection. Raccoons are relatively resistant and do not become infected with the fox strains. When searching my EndNote database, I cannot, however, find the specific paper. I found several others, probably from the same research group. Rich suggested wants to have a special twiv on rabies. I would love to hear more on pathogenesis and epidemiology of rabies in different countries. Perhaps you could invite Jane Smith if she's still alive.

1:27:36And Aldo is, as referenced above, in the Wengening Bio-Veterinary Research, Viral Infections and Pathology, and the FAO Reference Center for Foot and Mouth Disease. and your mention of end note kind of gave me a little jolt of trauma from grad school but yeah a special twiv on rabies would be very interesting many years ago we were doing historical papers of one sort or another and I thought Pasteur's publications he published something specifically on his rabies vaccine, as I recall. And the history of that in that paper would be interesting. But that's just background for what we're talking about.

1:28:25Yeah. I think, yeah, I would like to get someone on who knows everything about rabies viruses. Yeah, that'd be good. I don't know who that would be. By the way, I just asked AI about the measles question. And they said, no, there are not antibody escape mutants. And gave the same explanation about measles that we just did. And that is the fitness cost is too high. And there's actually only one. It's monotypic. There's only one strain worldwide and only, as far as we know, ever has been. Although, you know, with Riverside adding AI stuff, maybe it just data mined what we just said. I was thinking the same thing.

1:29:01Yeah, I think it's too fast. AI's been listening to us. Too fast. By the way, Alan, Columbia dropped its support of EndNote a couple of years ago. Because they used to pay for it and we all had it for free. and now you can't use it unless you want to pay for it yourself. But I don't write papers anymore. It's a horrible application. Nobody should use it. I'm sorry. That's my memory of it. But, you know, what did you use now? What are you using? Oh, there's a Firefox plug-in that I've used, and I've now forgotten it's an open source plug-in. I'm sure somebody can chime in with a note. Do you use Firefox all the time?

1:29:39Yeah, that's my default browser. I seldom have to track references because the type of writing I do, I'll just have the papers in a folder and I'm not expected to provide footnotes for what I'm writing. So Riverside works on Firefox. No, I had to install Chromium, which is a Linux version of Chrome, just to do this. You're such a nerd.

1:30:06Well, he's running Linux, right? I am. Like I said, he's a nerd. Yep, yep. And I love it, you know. Sure. Whatever floats your boat. What do you love about it? It's got no advertising. It's a big plus. Even when I switch to using, I've got a Mac still. It's a little laptop. And I switch to using it and Apple comes up with some, you know, Siri AI. Why haven't you activated it? It's like, no. Linux doesn't do that crap. Yeah. It just sits there, and unless I tell it to do something, it doesn't do it. So wait, if you go to a browser in Linux to a site, you don't get ads? Oh, well, that, yeah. So that's a separate problem.

1:30:50I do have an ad blocker installed in Firefox that's quite good. And what I will get is sites that say, you're using an ad blocker. Eight times out of 10, I can make that go away. And the other two times, I usually decide that the site probably isn't worth my time anyway.

1:31:12So, yeah. Gosh. But, I mean, just like the built-in operating system, the interface, it operates like an operating system should. It's not all commercialized. It's not at all commercialized. Yeah. Okay, let's do some pics of the week. Rich, what do you have for us? So this is inspired by my wife, as are several picks. By my wife and my cat, our cat. She found this, you know, something describing this, and of course being my own kind of nerd, I went up and looked at the original reference. And the reference is a PLOS One paper from, I don't know, a few years ago, that's titled The Effect of a Hiding Box on Stress Levels and Body Weight in Dutch Shelter Cats, a Randomized Controlled Trial, and has a Dutch team of scientists, okay?

1:32:10And anybody who has any familiarity with cats understands that cats love cardboard boxes. It just fascinates me. it's so amusing and in fact go on the internet this is not a domestic cat specific thing you can find pictures of tigers and lions and leopards uh sitting in cardboard boxes just a side note we um about a month ago we went to our local zoo which just got capybaras in and one of the one One of the exhibits walking in is the Bobcats and they have a couple of Amazon boxes just sitting in the Bobcat enclosure. And one of the Bobcats was curled up in it looking at us like a giant house cat.

1:32:57Yeah. So continue. So, you know, the big question is, well, why? What's this thing with boxes? And basically, they can feel a little concealed and hidden and secure. and this is a random controlled trial to if you like test that hypothesis where what the study was was they took uh 23 cats uh that they that just arrived at a shelter they set up a shelter to do this experiment um and typically when cats come to a shelter for whatever reason they've been abandoned or they're feral or whatever uh they're uh uh under a lot of stress for a period of time adjusting to their new circumstance. And they took half of these cats and in their confinement, and I think they did this individually with cats over time, in their particular space in the shelter, provided them with a cardboard box, and then the others did not.

1:33:59And then they have some rubric for assessing stress levels in the cat, and they also measured body weight as well. Didn't have any effect on body weight, all cats, regardless of whether or not you have a cardboard box lose weight when they adapt to the shelter. But according to their rubric measuring stress levels in cats which I looked up and is pretty interesting. I mean, how do you tell if a cat is stressed? It has to do with posture, what their ears look like. It's really subtle stuff But they have apparently a training video, and it all works. But basically, the cats with the cardboard boxes took about four days to adapt to the shelter.

1:34:51And the ones without the cardboard boxes took a couple of weeks. So it really had a pronounced effect. So I thought that was pretty cool. Excellent. So what is it about shelters that cats don't like? Oh, everything. Yeah, so I can speak to this. Go ahead. Speak to me. Yeah. First of all, it smells like the vet's office. Yeah. If they had that experience. Probably got dogs. It's got dogs. It's got people coming in and out. It's got a bunch of strange noises. It's not their home. Even if they were domesticated cats, they're used to their spots and none of that is there. They may be with other cats in a colony room.

1:35:31um it's just a it's a foreign environment and they really are by default they're not happy about it so uh after reading us and thinking about it it occurred to me so uh it's really a dilemma when we leave what to do with our cat okay because leaving him in the house all day without people he's so into people, I think would drive him nuts. Kennel's going to drive him nuts too, but we've discovered this kennel that was recommended by an only cat's vet in the area. This kennel was built by a veterinarian and built from the ground up, so it's not some adapted house or something. And the catatorium is this large rectangular room with, it could be as much as a 10 foot ceiling, I'm not sure, with, it'll house a dozen cats, unless they're cats that are housed together ordinarily, they can occupy the same enclosure.

1:36:38I'm not going to call it a cage, I'll call it an enclosure. There's six of these enclosures on each side that are a fairly wide mesh metal grid so you don't feel, you know, too confined. And the enclosures, that mesh goes from floor to ceiling and has a door that opens up into the central area. And each one has a big cat tree in it with all kinds of stuff in the cat tree and a bed and blankets and stuff and a window at the top of the cat tree. and so the cat can go into the enclosure and he's got a cat tree and he can climb up the cat tree he's got a window and the cat trees all have enclosures and they send us pictures of the cat every day and reproducibly the first couple of days the pictures are of ashy sitting in a box in the cat tree looking out, recovering from this experience, okay?

1:37:39And then all the subsequent pictures, twice a day, they open up the enclosure and the cats individually can walk out and play with the caretakers, okay? So from then on, he's out playing with this stuff. But it dawned on me, yeah, first couple of days, stress, he's going to go hide in his box. We have a pet sitter who comes. and yeah you have multiple cats right we have we currently have two um who both unfortunately hide from the pet sitter when she comes in um but at least they're they're in their home we don't have a we do have the local animal shelter which would be a very different experience and we have kennels but i'm not aware of anything quite as um luxurious as what you just do your Do cats like each other?

1:38:29Yes. Our current two cats, our third one is now on long-term loan to my mother-in-law and is very, very happy to be the only cat. Okay. She had made it clear that she wanted to be the only cat. Right. And now she's left these two knuckleheads behind. And Theo and Oliver get along great. They're buddies. So when you're gone, they've got each other. They've got each other. That's good. Yeah. Yeah. Okay. Alan, what do you have for us? That was quite a pick. Yeah. So I have something. It seemed a little bit Halloween appropriate, but also we have the holiday gift giving season coming up. So if you're familiar with Edward Gorey, he drew these Victorian line art style cartoons that were typically very dark in their humor.

1:39:28And this is his take on a tarot card deck. It's called the Fantod Pack. Fantod is anxiety. and it's very well done in his typical dark style and you can draw cards from it and try to decide how bleak your future is. This looks great. Fun gift. How many cards in the deck? I think it's 20. So it's not a full... Tarot deck is like 50-something or I don't know. So it is a limited set, but they're all quite good. Yeah, the examples are quite entertaining. Yes. Cool. That's pretty cool. Yeah, I like Gory. I love his books. I had to look him up. I was unfamiliar with him. He sounds like an interesting character.

1:40:25Get the Gashley Crumb Tinies and the Insect God, and you'll have a pretty good. Okay. Yeah. My pick is a nice document put out by the Welcome Trust. It's entitled Welcome Global Monitor 2026, Trust in Science Under Pressure. This is a 60-page document you can get as a PDF. It's free. And it's all about the state of public trust in science. and it's an extensive survey and also essay, basically. And they have key findings, right? I'm going to just tell you about the key findings that they summarize. First, trust in science and scientists has fallen since the COVID-19 pandemic. And they do it in multiple regions, not just the U.S.

1:41:23And you can dive into the numbers and so forth. Number two, trust in science is associated with stronger, more equal societies. So trust in science is lowest among those who feel they are struggling to get by. Not surprising, right? People who feel systems are working for them are more likely to trust science. And people with positive health care experience are also having more trust with science. We have an overall number here. Confidence in national institutions is another key. Yes. Contributor. In 2025, 72 % of people reported some or a lot of trust in science compared with 80 % in 2020 and 77 % in 2018.

1:42:08So those are the numbers. So key finding number three, trust is higher among people who see science as relevant and beneficial. Like listeners of TWIV, right? Most people in the world do not feel that science benefits everyone equally.

1:42:27I think most people in the world have a cell phone. So that's science, folks. People with more trust in science are more positive about its benefits. In countries where trust in science is widespread, low trust groups tend to be further apart from others in their attitudes to science. So those are the three key findings. And then it's a very long document. So it's the world's largest study of public trust in science. It has data from 140 ,000 adults in 140 countries. It's a really unique data set. And I think you ought to take a look at it. It's really good. The only thing that I want to say is trust in science has been eroded by people who are anti-science and very visible.

1:43:15Like the anti-vax crowd is a visible part of people who have degraded science incorrectly and by lying about it. And I just think that's unfortunate and that's part of the decline. And also COVID was as well because people thought we overreached and so forth in COVID. But, you know, we didn't know what to do, okay? We were just trying to get by. So I don't think that's exactly fair. But the other findings here are valid in some of the things I said. Trust in science has fallen more than trust in other groups and institutions. But, you know, folks, even if you think science doesn't help you it really does uh this is uh this is one of the uh charts i like best in this just looking through it is this there's a chart that plots a percent of people questioned with a lot of trust in science versus a percent of people who feel the most benefit from the work of science.

1:44:19To me, it's just, in a way, it's a way of just charting by location, because each dot is a different location, what the level of trust in science is. And you can look at the table, but you can't sort it, okay? It's alphabetical. But if you look at the chart if you hover over any of the dots it tells you where it came from and the u.s is uh surprisingly in a way high on the chart 53 with a lot of trust in science 57 percent uh think the work of scientists benefits most people at the top is finland with 66 and 76 96%. On the bottom, ooh. Somalia. 9 % have a lot of trust in science. 9 % work of scientists benefits most people.

1:45:22Congo is down there. Ecuador. Albania. Peru. This is very, very interesting. Really interesting. I wonder if they ever asked them to give examples of ways that you think science might help you. Because I think a lot of people don't know how science helps them, actually. I think a lot of people at the bottom end of this chart are dealing with more pressing concerns, like not getting machine gunned on the way to school in the morning. Good point. I understand that. But anything they have that's good is probably from science. And a lot of what they have that's bad is from science, too. Yeah, the machine guns are from science, too.

1:46:06Yeah, exactly. Good point. This is interesting. Anyway, figure one is cool. It's a heat map of people who trusted science a lot. And, you know, North America, parts of Europe. There's a country in Central Asia there. I don't know which one that is. It has a lot of trust in science. Anyway, you should read it. Very interesting. It's really good. It's very interesting. Well done, study. We have a listener pick from Anne. I'm almost finished reading this book, Blockers, by Michael Lewis. Lewis is well known for several of his books, including Moneyball and The Big Short, which was made into a movie.

1:46:44If you haven't seen it, it's very much worth the time. This book is by turns engaging and infuriating as it describes the competent, experienced folks who were removed or otherwise impeded in their work for the U.S. government thanks to DOGE, the implementations of Project 2025, and the inept, power-hungry heads of various departments. I've just finished the penultimate chapter about Francis Collins, where Lewis, with Collins, tries to determine who was responsible for forcing Collins out, since that was never explicitly made clear to him. Reading that chapter will lay out the possible motives several well-known people might have had to remove him, and one stands out.

1:47:25Like his previous book, Who is Government?, Lewis does a great job explaining the work of dedicated civil servants. I can highly recommend both. Anybody read this book? I have not read it. Anything by Michael Lewis? I've read Moneyball, and I saw Lewis interviewed on the PBS NewsHour about this book.

1:47:50cool cool all right that is twiv 1371 you can find show notes at microbe.tv slash twiv if you have any questions or comments or picks of the week we'd love to get them twiv at microbe.tv if you enjoy these programs we'd love your support microbe.tv slash contribute alan dove is at alan dove.com turbidplack.com thank you alan thank you it's always a pleasure. Rich Condit is an emeritus professor, University of Florida, Gainesville. He is currently in Austin, Texas. Thank you, Rich. Sure enough, always a good time. I wonder how much cat email we're going to get. Probably some. Probably some. I'm Vincent Racaniello.

1:48:33You can find me at microbe.tv. I'd like to thank the American Society for Virology and the American Society for Microbiology for their support of TWIV, Ronald Jenkes for the music, and Jolene Ramsey for the timestamps. You've been listening to This Week in Virology. Thanks for joining us. We'll be back next week. Another TWIV is viral.