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In the Journals: Recent (Yet to Be Reproduced) Data Increase Concerns about Circulating H5N1

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In the Journals: Recent (Yet to Be Reproduced) Data Increase Concerns about Circulating H5N1
July 25, 2024

On June 28, 2024, researchers at the University of Wisconsin, Madison, published a paper that, if reproduced by other laboratories, was worrisome (Eisfeld, AJ, Biswas A, Guan L, et al. “Pathogenicity and Transmissibility of Bovine H5N1 Influenza Virus,” Nature. 2024 Jul 8. doi: 10.1038/s41586-024-07766-6.) The study involved a particular strain of H5N1 influenza virus (commonly referred to as “bird flu”) that has caused a handful of infections among dairy workers in the United States.

The most important protein of influenza virus is the hemagglutinin (or H protein), which attaches the virus to cells that line the windpipe, large breathing tubes and lungs. But influenza virus doesn’t have only one type of hemagglutinin, it has 16. Bird flu is hemagglutinin type 5 (or H5). Although H5 viruses can rarely cause severe and fatal disease in people, spread of H5 viruses from person to person is extremely poor. Only three types of influenza hemagglutinins have ever caused pandemic disease in people: H1, H2 and H3. H5 viruses, on the other hand, have circulated for decades and have never caused a human pandemic. Why? 

H1, H2 and H3 influenza viruses bind to a receptor on cells called alpha-2,6 sialic acid. This receptor is located on cells of the upper and lower respiratory tract of people. H5 influenza viruses, on the other hand, don’t bind to the alpha-2,6 sialic acid receptor; they bind to the alpha-2,3 sialic acid receptor. Unlike humans, birds have this type of binding receptor throughout their respiratory tracts. And cows have this receptor on their udders. This is why H5 viruses can cause pandemics in birds and cows. But H5 viruses don’t cause pandemics in humans.

Researchers at the University of Wisconsin, Madison, have now identified a strain of H5N1 virus that was detected in cows that now binds to the alpha-2,6 sialic acid receptor. Further, they found that the virus could reproduce in the upper respiratory tract of ferrets, which mimic human respiratory tracts. Fortunately, the virus wasn’t easily transmitted from one ferret to the next. But this is an unsettling development and will require continued surveillance to make sure that the H5N1 strain currently circulating in cows and poultry doesn’t evolve to become a human pandemic.

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