PB2 E627K mutation

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The PB2 E627K mutation in the viral polymerase of H5N1 (colloquially known as bird flu) allows for interaction with the mammalian gene ANP32A [1] for optimal viral replication. [1] Such host switching can be of grave public health concern. [2] [3] [4] It was first noted in the scientific literature in February 2014, [5] and emerged in the then-novel highly pathogenic avian influenza A(H5N1) clade in 2020. [6] Host adaptation has been noted as being "rapid"; [7] the most recent outbreak was posited to be in San Bernardino County, California dairy cow herds in March 2025. [8]

Nomenclature

Following the standard format in virology, PB2 refers to the PB2 protein, E to glutamic acid (the original amino acid), 627 to its position in the PB2 protein sequence, and K (lysine) the amino acid mutation replacing the default glutamic acid. [9]

References

  1. 1 2 "GISAID - Highly Pathogenic Avian Influenza Outbreak in the United States". gisaid.org.
  2. ↑ Robinson-McCarthy, Lindsey R.; Zirckel, Kylie E.; Simmons, Holly C.; Le Sage, Valerie; McCarthy, Kevin R. (February 27, 2025). "A replicating recombinant vesicular stomatitis virus model for dairy cattle H5N1 influenza virus glycoprotein evolution". BioRxiv: The Preprint Server for Biology: 2025.02.27.640582. doi:10.1101/2025.02.27.640582. PMC   11888439 . PMID   40060653.
  3. ↑ Uyeki, Timothy M.; Milton, Scott; Hamid, Cherissa Abdul; Webb, Cynthia Reinoso; Presley, Steven M.; Shetty, Varun; Rollo, Susan N.; Martinez, Diana L.; Rai, Saroj; Gonzales, Emilio R.; Kniss, Krista L.; Jang, Yunho; Frederick, Julia C.; Cruz, Juan A. De La; Liddell, Jimma; Di, Han; Kirby, Marie K.; Barnes, John R.; Davis, C. Todd (June 5, 2024). "Highly Pathogenic Avian Influenza A(H5N1) Virus Infection in a Dairy Farm Worker" . New England Journal of Medicine. 390 (21): 2028–2029. doi:10.1056/NEJMc2405371. PMID   38700506 – via Taylor and Francis+NEJM.
  4. ↑ "ALERT: Deadly H5N1 Mutation Found in US Dairy Herds—Pandemic Risk Rising". March 13, 2025.
  5. ↑ Jonges, Marcel; Welkers, Matthijs R. A.; Jeeninga, Rienk E.; Meijer, Adam; Schneeberger, Peter; Fouchier, Ron A. M.; de Jong, Menno D.; Koopmans, Marion (February 13, 2014). "Emergence of the Virulence-Associated PB2 E627K Substitution in a Fatal Human Case of Highly Pathogenic Avian Influenza Virus A(H7N7) Infection as Determined by Illumina Ultra-Deep Sequencing". Journal of Virology. 88 (3): 1694–1702. doi:10.1128/JVI.02044-13. PMC   3911586 . PMID   24257603.
  6. ↑ Marchenko, Vasiliy Yu; Panova, Anastasia S.; Kolosova, Natalia P.; Gudymo, Andrey S.; Svyatchenko, Svetlana V.; Danilenko, Alexey V.; Vasiltsova, Natalia N.; Egorova, Marina L.; Onkhonova, Galina S.; Zhestkov, Pavel D.; Zinyakov, Nikolay G.; Andreychuk, Dmitriy B.; Chvala, Ilya A.; Kosenko, Maksim N.; Moiseeva, Anastasia A.; Boldyrev, Nikita D.; Shadrinova, Kiunnei N.; Perfilieva, Olga N.; Ryzhikov, Alexander B. (November 3, 2024). "Characterization of H5N1 avian influenza virus isolated from bird in Russia with the E627K mutation in the PB2 protein". Scientific Reports. 14 (1): 26490. Bibcode:2024NatSR..1426490M. doi:10.1038/s41598-024-78175-y. PMC   11532466 . PMID   39489822.
  7. ↑ Liu, William J.; Li, Jun; Zou, Rongrong; Pan, Jingcao; Jin, Tao; Li, Liqiang; Liu, Peipei; Zhao, Yingze; Yu, Xinfen; Wang, Haoqiu; Liu, Guang; Jiang, Hui; Bi, Yuhai; Liu, Lei; Yuen, Kwok-Yung; Liu, Yingxia; Gao, George F. (September 22, 2020). "Dynamic PB2-E627K substitution of influenza H7N9 virus indicates the in vivo genetic tuning and rapid host adaptation". Proceedings of the National Academy of Sciences. 117 (38): 23807–23814. Bibcode:2020PNAS..11723807L. doi: 10.1073/pnas.2013267117 . PMC   7519270 . PMID   32873642.
  8. ↑ "Bird flu-infected San Bernardino County dairy cows may have concerning new mutation". Los Angeles Times. March 12, 2025.
  9. ↑ "DeepSeek".
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