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Michael Worobey Profile picture
@MichaelWorobey
Apr 26 • 10 tweets • 2 min read • Read on X
Important update on metadata of H5N1 in cattle (and back to birds):

Thanks to the extraordinary detective skills of @flodebarre, we are pleased to be able to share this table containing locations and dates for several H5N1 cases in cattle and birds:

github.com/andersen-lab/a…
We have pseudomized specific location data relating to individual farms/herd/operations, and are only sharing location to state.
We are now incorporating this important metadata into our phylogeographic analyses, which will allow us to do things like use "local molecular clocks" of the sort that Andrew Rambaut and I previously used to resolve the deep history of influenza A virus:

nature.com/articles/natur…
Sidebar: this paper also discusses the "Great Epizootic of 1872".

Haven't heard of it? It's a fascinating story.
We will also be attempting to pin down the most likely location of origin of this outbreak,. And we are integrating sequence, timing, and geographical information to investigate how these viruses have moved and are moving within and between states.
Please note that, in addition to the metadata, the consensus sequences from our genome assemblies of the 239 cases times 8 genome segments are publicly downloadable from our github.

As our our sequence alignments.

github.com/andersen-lab/a…
Thanks to Andy Bowman and @Jimpigvet for sharing consensus genomes from H5N1 cases they sampled in Ohio.
And to all the people collaborating on our efforts, including @xrayfoo @flodebarre Kristian Andersen @LouiseHMoncla @swientist @meera_chand @MOUGK @EvolveDotZoo @stgoldst @stuartjdneil @PeacockFlu Andrew Rambaut @angie_rasmussen @suchard_group @LemeyLab @jepekar @josh__levy
Joel Wertheim @LrnM9 @evogytis Daniel Goldhill Chris Ruis

As well as @USDA_APHIS for making their SRA data available, and all the veterinarians, farmers, farmworkers, and others doing the boots-on-the ground work here.
@jimpigvet And thanks to Rich Webby too!

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More from @MichaelWorobey

Michael Worobey Profile picture
Apr 26
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). Image
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.
@PeacockFlu was the first person I know of who homed in on how interesting this human's virus was, in the context of the cattle H5N1 outbreak, in this piece by @HelenBranswell.

statnews.com/2024/04/23/h5n…
Read 28 tweets
Michael Worobey Profile picture
Apr 26
Into the weeds:

One reason it is particularly frustrating that full metadata has not been shared for genome sequences my colleagues and I have assembled from raw sequence read data released by @USDA / @USDA_APHIS, is that without those dates...
it is not possible to test some really important hypotheses.

Years ago, staring long enough (weeks) at evolutionary trees of all 8 flu A genomes segments that stored on my kitchen table, it finally occurred to my brain that you can't just assume that these viruses evolve...
at the same rate in each host species. Andrew Rambaut and I devised a "local molecular clock" to allow the virus molecular clock to tick at a different rates in each host species.
Read 6 tweets
Michael Worobey Profile picture
Apr 24
A few thoughts on the role of pigs in the emergence of influenza A virus in mammals.

1. It is simply not the case that movement of flu viruses into non-swine mammal species requires pigs as a "mixing vessel".
2. Here is a list of mammalian influenza A lineages that *did not* require the involvement of pigs:

Canine flu
Equine flu
Phocine flu
Now bovine flu.
I'll save you a google search: "phocine" = seals/sea lions.
3. Pigs are tested routinely for flu in the US and it is likely that H5N1 would have been detected by now if it was circulating in pigs (h/t @swientist).

4. A big push to screen asymptomatic cattle, and those who work in close contact with them, is important right now.
Read 4 tweets
Michael Worobey Profile picture
Apr 24
So, *preliminary* molecular clock analyses indicate that the time of the most recent common ancestor (TMRCA) of the US cattle flu clade was late December.

TMRCA of that clade and the closest relatives in birds, mid-December.

If single intro, likely between those rough dates. Image
Team effort:

@xrayfoo @flodebarre Kristian Andersen @LouiseHMoncla @swientist @meera_chand @MOUGK @EvolveDotZoo @stgoldst @stuartjdneil @PeacockFlu Andrew Rambaut @angie_rasmussen David Robertson @suchard_group @LemeyLab @jepekar @josh__levy Joel Wertheim @LrnM9 Image
@xrayfoo @flodebarre @LouiseHMoncla @swientist @meera_chand @MOUGK @EvolveDotZoo @stgoldst @stuartjdneil @PeacockFlu @angie_rasmussen @suchard_group @LemeyLab @jepekar @josh__levy @LrnM9 More details to follow, but sincere thanks to scientists @USDA and contributors to @GISAID for making this possible.
Read 4 tweets
Michael Worobey Profile picture
Apr 23
OK, I think we're close to decisive evidence that US bovine H5N1 had a single origin from birds, and that when related viruses from birds *have* been found, they are jumps from cattle back into birds.

Grackles, blackbirds, chickens all show mammalian adaptation like PB2 M631L. Image
My understanding is that these bird (and cat) viruses within the "bovine" clade were sampled from farms that had bovine H5N1.

So, are the birds on these farms giving this virus to the cattle, or are the cattle giving it to the birds? It is cattle to birds very likely.
There is just no good reason to think there's an epizootic of mammalian adapted H5N1 in birds.
Read 5 tweets
Michael Worobey Profile picture
Apr 23
Here is a link to 239 consensus genome sequences, assembled by @xrayfoo, from sequencing reads of 2.3.4.4b H5N1 influenza A virus from cattle and other species.

github.com/andersen-lab/a…
We very grateful to the scientists @USDA / @USDA_APHIS for their release of the important raw data from which these sequences were inferred:

ncbi.nlm.nih.gov/bioproject/PRJ…
In addition to @xrayfoo, thanks to @LrnM9, @flodebarre, Kristian Andersen, Andrew Rambaut, @MOUGK , @EvolveDotZoo, @swientist, Marc Suchard, @PeacockFlu, and others.
Read 14 tweets

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