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.
Andrew, my student Guan-Zhu Han, and I published a paper showing that when this empirical reality was included in our models, the picture of the deep history of these viruses, which had been hopelessly confusing, snapped into focus:
My concern at the moment is that H5N1 might evolve at a different rate in cattle than in birds. And until we have the sampling dates for the cattle viruses, we won't know if it is faster or slower (or the same) in cattle and birds.
And that means the outbreak could be somewhat older or younger than our current estimates.
We want to be able to understand, ASAP, how this cattle outbreak originated and what is full consequences might be.
And we have at least one hand tied behind our back at the moment.
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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.
@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.
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:
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:
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.
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.
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
@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.
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.
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.
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.
In addition to @xrayfoo, thanks to @LrnM9, @flodebarre, Kristian Andersen, Andrew Rambaut, @MOUGK , @EvolveDotZoo, @swientist, Marc Suchard, @PeacockFlu, and others.