Thread by @kakape

With #H5N1 #birdflu spreading amongst dairy cows, one of the most important things to think about right now is what would need to happen for this virus to actually start a pandemic.
I'm on a train, so a brief thread...

One thing to remember is that compared to some other influenza viruses H5N1 actually faces pretty high barriers to becoming a human-to-human pathogen. I wrote a story a little over a year ago outlining some of the changes it would probably need: science.org/content/articl…

As @PeacockFlu told me at the time: H5 probably has one of the largest barriers to being a pandemic virus of any avian influenza virus. “It's really wrong in so many ways”, he told me.

But as @PeacockFlu also pointe out: “Obviously it only has to get the right combination of mutations once to jump.”
Getting that combination may be the virus’ equivalent of winning the lottery, but with millions and millions of viral particles in a milliliter of milk, boy oh boy is this virus buying a lot of lottery tickets.

@PeacockFlu That’s what Martin Beer meant when he told me recently: “Nobody wants this dangerous virus to become entrenched in a new species that we use to produce food and that has so much close contact to humans.”

@PeacockFlu In theory there is a shortcut for the virus to acquire a lot of changes at once and that is reassortment: The influenza genome is made up of 8 separate segments and when two different viruses infect the same cell they can get reshuffled like two decks of cards coming together.

This is why researchers have always been worried a lot about pigs. They can get infected with both human and avian influenza viruses and are sometimes called “mixing vessels” because of that.
And this is where a recent preprint on the receptors in cows’ udders comes in.

The authors show that a cow’s mammary gland contains both duck-type and human-type flu receptors (sialic acids, more about them another time). And they write that this shows that “cattle have the potential to act as a mixing vessel” for new flu viruses.

biorxiv.org/content/10.110…

Most researchers I've talked to are pretty skeptical of this idea, however. For the udder to function as a mixing vessel, you would have to have the same cells infected by H5N1 and a human flu virus. As far as we can tell that is highly unlikely.

Even Richard Webby, one of the preprint's authors, agreed with this when I talked to him. “The possibility is there, but you’re dead right, it’s a pretty rare occurrence, I'd think, even this outbreak.”
In more than 25 years of studying H5N1 this is the first time it had been seen in a cow’s udder, he noted.

But that doesn’t mean that the presence of both types of receptors does not pose a risk for the virus adapting over time to the human receptor.
As @PeacockFlu told me there is a pattern in some species that have both receptors for the virus to adapt (in the long-term, not the short-term!) to the second one. “It seems a good reason to get this eradicated from cattle as soon as possible.”
science.org/content/articl…

The point of all this is that there are ways we can see that the virus might start to change in exactly the ways we don’t want it to change. That might not happen tomorrow or next week, but the longer it spreads and replicates, the more likely it is to happen.

And that's just what we know. Until a few weeks ago no-one anticipated that cow’s udders would have these two types of receptors and that avian flu would grow so well there.

And as @Helenbranswell points out in this great piece, that is the whole point of our experience with this virus: It keeps surprising us.
statnews.com/2024/05/09/bir…