ArticleProceedings of the National Academy of Sciences of the United States of America2009
Adaptive strategies of the influenza virus polymerase for replication in humans.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 252 papers.
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252 citing papers in PubMed, 392 citations in OpenAlex.
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- Emergence of mammalian-adaptive PB2 mutations enhances polymerase activity and pathogenicity of cattle-derived H5N1 influenza A virus.Nature communications · 2025Article
- Evolutionary trajectories and zoonotic potential of a PB2 mutation triad (I147T, K339T, and A588T) in avian influenza viruses.Veterinary research · 2025Article
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- Recent advances in avian influenza virus: Molecular pathogenesis, emerging strains, and next-generation therapeutics.World journal of virology · 2025Review
- Heat shock protein A1L restricts influenza A virus by ubiquitination of NA.Journal of virology · 2025Article
- Mammalian ZAP and KHNYN can independently restrict CpG-enriched avian viruses.bioRxiv : the preprint server for biology · 2025Article
- Decoding non-human mammalian adaptive signatures of 2.3.4.4b H5N1 to assess its human adaptive potential.Microbiology spectrum · 2025Article
- Glutamic Acid at Position 343 in PB2 Contributes to the Virulence of H1N1 Swine Influenza Virus in Mice.Viruses · 2025Article
192 more citing papers are in PubMed but not listed here.
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2 authors at 1 institution in 1 country.
Funding
Abstract
Transmission of influenza viruses into the human population requires surmounting barriers to cross-species infection. Changes in the influenza polymerase overcome one such barrier. Viruses isolated from birds generally contain polymerases with the avian-signature glutamic acid at amino acid 627 in the PB2 subunit. These polymerases display restricted activity in human cells. An adaptive change in this residue from glutamic acid to the human-signature lysine confers high levels of polymerase activity in human cells. This mutation permits escape from a species-specific restriction factor that targets polymerases from avian viruses. A 2009 swine-origin H1N1 influenza A virus recently established a pandemic infection in humans, even though the virus encodes a PB2 with the restrictive glutamic acid at amino acid 627. We show here that the 2009 H1N1 virus has acquired second-site suppressor mutations in its PB2 polymerase subunit that convey enhanced polymerase activity in human cells. Introduction of this polymorphism into the PB2 subunit of a primary avian isolate also increased polymerase activity and viral replication in human and porcine cells. An alternate adaptive strategy has also been identified, whereby introduction of a human PA subunit into an avian polymerase overcomes restriction in human cells. These data reveal a strategy used by the 2009 H1N1 influenza A virus and identify other pathways by which avian and swine-origin viruses may evolve to enhance replication, and potentially pathogenesis, in humans.
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