Preprint: An Emerging PB2-627 Polymorphism Increases the Pandemic Potential of Avian Influenza

Flu Virus binding to Receptor Cells – Credit CDC

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A preprint - published 2 days ago on the bioRxiv server - has been getting a lot of attention as it reports on an increasing incidence of a PB2-627V mutation in avian flu viruses, which increases their ability to bind to mammalian receptor cells, while continuing to bind to avian cells. 

We've discussed the importance of mammalian adaptation of avian flu viruses often, but briefly:

• Human adapted influenza viruses have an RBS - Receptor Binding Site (the area of its genetic sequence that allows it to attach to, and infect, host cells) that – like a key slipping into a padlock -`fit’ the receptor cells commonly found in the human upper respiratory tract; the alpha 2,6 receptor cell.

• Avian adapted flu viruses, like the H5N1 virus, bind preferentially to the alpha 2,3 receptor cells found in the gastrointestinal tract of birds.

• While there are some alpha 2,3 cells deep in the lungs of humans, for an influenza to be successful in a human host, most researchers believe it needs to be able to bind to the a 2,6 receptor cell. 

Since the copyright notice is somewhat restrictive, I've posted the link below and would encourage everyone to read the abstract, and many will want to continue on to read the full 29-page paper. 

An emerging PB2-627 polymorphism increases the pandemic potential of avian influenza virus by breaking through ANP32 host restriction in mammalian and avian hosts

Yuxin Guo, Sicheng Shu, Yong Zhou, Wenjing Peng, Zhimin Jiang, Yudong Li, Tian Li, Fanshu Du, Linlin Wang, Xue Chen, Jinze Dong, Chuankuo Zhao, Maggie Haitian Wang, Yipeng Sun, Honglei Sun, Lu Lu, Paul Digard, Kin-chow Chang, Hui-Ling Yen, Jinhua Liu, Juan Pu

doi: https://doi.org/10.1101/2024.07.03.601996

 You can also listen to a very brief audio presentation on ScienceCast.

The authors report that this PB2-627V mutation not only maintains viral fitness in poultry, it facilitates the aerosol transmission of AIVs between ferrets. The concern is, this mutation could go a long way in overcoming the `species barrier' between avian and mammalian-adapted influenza viruses.

Until the middle of the last decade this was a fairly rare mutation - and mostly seen in LPAI H9N2 viruses - but it has now been found in at least 10 avian flu subtypes, including a handful of H5N1 clade 2.3.4.4b samples.

A different mutation - PB2-627K - has long been monitored since it increases the ability of avian flu viruses to replicate in a mammalian host, but it is usually only seen in mammals (see Mammalian Adaptation in the PB2 Gene of Avian H5N1 Influenza Virus).

The authors now suggest - given the rising incidence of PB2-627V - that it could be used as a molecular marker to assess the pandemic potential of avian flu viruses while they are remain in an avian host.

While it seems likely that multiple complementary amino acid changes would be needed to turn an avian influenza virus into a fully humanized pathogen, this mutation appears to provide the virus a significant advantage. 

Stay tuned.