Scientists have identified three key changes needed to adapt the H5N1 avian influenza virus to mammals.
has also sickened and killed a menagerie of mammals, raising fears it might evolve to spread more efficiently between these animals, and ultimately between people.
So exactly how would this virus have to mutate to cause a human pandemic? Scientists can’t fully answer that yet—but they have identified some key steps. Much of what is known comes from controversial experiments more than a decade ago in which researchers coaxed an earlier strain of H5N1 to spread more efficiently between ferrets.
It seems an easy step. H5N1 has managed it several times already in the current avian flu virus outbreak. For instance, researchers found the E627K mutation in infected foxes that were sampled in the Netherlands in late 2021 and early 2022. The mutation was also found in a sample from a New England seal, part of an outbreak of H5N1 in seals off the East Coast last year. The PB2 mutations don’t seem to hamper the virus in birds, Richard says.
Another crucial hemagglutinin change would make H5N1 more transmissible through the air—also a prerequisite for a pandemic. Once the virus attaches to a cell it is taken up into a vesicle that becomes more acidic, triggering a pH-dependent shape change in the hemagglutinin. This leads the virus and vesicle membranes to fuse, letting the pathogen’s genetic material escape into the cell. In water, the hemagglutinin on avian viruses typically has no problem staying untriggered.
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