We need to talk about that human case of H5N1 in Texas... Here is a bootstrapped (NJ) tree showing how the closest realtive of H5N1 sampled in cattle is a virus the infected an male individual who reportedly worked on a farm with cattle (dairy, I believe).
I used all-8-genome-segment concatenated sequences for this analysis, with the help of @evogytis, for this, for maximum signal. Bootstrap values show strong support for the (human + cattle) grouping.
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<Start text from Helen's article:> “If you look at all the cattle sequences together, they all cluster, as do the cats and the chickens and the grackles and stuff.” “The thing that doesn’t fit that picture is the human case,” he said.
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The genetic sequence from the human case, which occurred on an unidentified farm in Texas, is sufficiently different from the cattle sequences that it can’t be easily linked to them, he said.
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The differences suggest that the individual was either infected in a separate event — maybe not via a cow, but through contact with infected wild birds — or that there might have been another line of viruses in cattle early on and it has since died out.
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“It’s basically too distant a cousin to be connected directly to this outbreak, which either means it’s a second spillover or there was an early bifurcation of the cattle sequences,” Peacock said. <End text from Helen's article:>
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We now know that this individual was a dairy farm worker who worked in a geographical area with cattle with symptoms consistent with H5N1...but it appears that no samples were collected (!) from cattle from the farm where he worked:
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Rosemary Sifford, USDA's chief veterinarian, said in a briefing yesterday: "The fact that the human who was sampled has a sequence that appears to be a predecessor to those that we have found in cattle -- our interpretation at this point...
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"is that that means likely that person became infected through a herd that we did not receive any samples from for testing," "There were herds that had clinical signs in that geographic area before we had the first herd that we had positive H5N1 test results in.
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"That, we think, is the strongest hypothesis at this time with regard to the infection for that person. We collaborate closely with the CDC and local public health for the human testing. We are not directly involved with that."
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Quick detour into evolutionary biology: It is close, but not quite right, to call a virus sampled in late March, from a human likely infected by a cattle virus, a "predecessor" to those we have found in cattle at around the same time point.
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My colleagues and I preliminarily estimate that the viruses sampled to date, and pictured in the phylogenetic (evolutionary) tree at the top of this thread, had a common ancestor (in cattle) that existed in December or January. The human virus in the Texas farm worker...
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was not sampled until March. So it can't be a predessor. Let's use humans and chimps to illustrate. Both chimps and humans exist in the present. Their predessor existed some 5 million years ago, and was neither a chimp nor a human.
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The predessor population eventually split into two separate lineages: one that led to chimps, the other to humans.
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Each lineage accumulated distinct genomic mutations over the last 5 million years. The mutations in humans led to adaptions (like huge and powerful brains) that gave humans a big advantage over chimps. There are now billions of humans, and only a few hundred thousand chimps.
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I believe the combined evidence (especially that this person likely became infected from cattle) points strongly in favour of the hypothesis that the human virus and the current sample of cattle virus are descendents of a single jump of H5N1 from birds into cattle.
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Cats, chickens, blackbirds and grackles on farms with sick cattle are all getting infected by spillback. This human is no different, likely. I suspect that we will find, as the number of sequenced cattle viruses grows, ones on the same branch of the tree that led to this human.
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The interesting thing is that we can, and are, dissecting the mutations represented by the asterisks on the H5N1 tree. We konw what they are, several are indeed likely to provide adaptive benefits to the viruses in mammals.
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And I suspect the ones on the branch that led to the human case in Texas just can't compete with the "main" cattle H5N1 lineage. The main bovine lineage may be, to innumerable humans, what the minor lineage is to the few chimps who have managed to survive to present.
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If correct, this drives the cattle H5N1 lineage even further back than we had thought, though we may not see the date of the bird to cattle cross-species transmission event change much.
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It would be good if samples, perhaps environmental samples, could be collected from that farm to directly test these hypotheses.
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One last thing - this suggests, but does not prove, that the common ancestor of both the main, and putative minor, bovine H5N1 lineages existed in Texas.
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Please check at @LouiseHMoncla's analysis on the relevant mutations, on the @nextstrain platform! x.com/LouiseHMoncla/status/1…
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But looping back to @PeacockFlu 's thoughts in the @statnews article, it is still possible that this does represent an independent jump from the avian reservoir into cattle.
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@influenzal notes that there are no mammalian-adaptive substitutions in common between the viruses that have been sampled in cows and the virus in the Texas patient.
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And more complex scenarios exist. Joel Wertheim and I have noticed that the Texas human H5N1 virus might be a reassortant. Its HA, PB2, and NP all appear to sit basal to the current sample of cattle H5N1, while the other 5 segments appear to sit within the cattle clade.
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Apr 27, 2024 · 11:33 AM UTC

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