PB2 E627K mutation

The PB2 E627K mutation in the viral polymerase of H5N1 (colloquially known as bird flu) allows for interaction with the mammalian gene ANP32A{{Cite web|url=https://gisaid.org/resources/gisaid-in-the-news/highly-pathogenic-avian-influenza-outbreak-in-the-united-states/|title=GISAID - Highly Pathogenic Avian Influenza Outbreak in the United States|website=gisaid.org}} for optimal viral replication. Such host switching can be of grave public health concern.{{Cite journal|title=A replicating recombinant vesicular stomatitis virus model for dairy cattle H5N1 influenza virus glycoprotein evolution|first1=Lindsey R.|last1=Robinson-McCarthy|first2=Kylie E.|last2=Zirckel|first3=Holly C.|last3=Simmons|first4=Valerie|last4=Le Sage|first5=Kevin R.|last5=McCarthy|date=February 27, 2025|journal=BioRxiv: The Preprint Server for Biology|pages=2025.02.27.640582|doi=10.1101/2025.02.27.640582|pmid=40060653|pmc=11888439 }}{{Cite journal|url=https://www.nejm.org/doi/full/10.1056/NEJMc2405371|title=Highly Pathogenic Avian Influenza A(H5N1) Virus Infection in a Dairy Farm Worker|first1=Timothy M.|last1=Uyeki|first2=Scott|last2=Milton|first3=Cherissa Abdul|last3=Hamid|first4=Cynthia Reinoso|last4=Webb|first5=Steven M.|last5=Presley|first6=Varun|last6=Shetty|first7=Susan N.|last7=Rollo|first8=Diana L.|last8=Martinez|first9=Saroj|last9=Rai|first10=Emilio R.|last10=Gonzales|first11=Krista L.|last11=Kniss|first12=Yunho|last12=Jang|first13=Julia C.|last13=Frederick|first14=Juan A. De La|last14=Cruz|first15=Jimma|last15=Liddell|first16=Han|last16=Di|first17=Marie K.|last17=Kirby|first18=John R.|last18=Barnes|first19=C. Todd|last19=Davis|date=June 5, 2024|journal=New England Journal of Medicine|volume=390|issue=21|pages=2028–2029|via=Taylor and Francis+NEJM|doi=10.1056/NEJMc2405371|pmid=38700506 |url-access=subscription}}{{Cite web|url=https://munsifdaily.com/deadly-h5n1-mutation-found-in-us-dairy-herds/|title=ALERT: Deadly H5N1 Mutation Found in US Dairy Herds—Pandemic Risk Rising|date=March 13, 2025}} It was first noted in the scientific literature in February 2014,{{Cite journal|title=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|first1=Marcel|last1=Jonges|first2=Matthijs R. A.|last2=Welkers|first3=Rienk E.|last3=Jeeninga|first4=Adam|last4=Meijer|first5=Peter|last5=Schneeberger|first6=Ron A. M.|last6=Fouchier|first7=Menno D.|last7=de Jong|first8=Marion|last8=Koopmans|date=February 13, 2014|journal=Journal of Virology|volume=88|issue=3|pages=1694–1702|doi=10.1128/JVI.02044-13|pmid=24257603 |pmc=3911586 }} and emerged in the then-novel highly pathogenic avian influenza A(H5N1) clade in 2020.{{Cite journal|title=Characterization of H5N1 avian influenza virus isolated from bird in Russia with the E627K mutation in the PB2 protein|first1=Vasiliy Yu|last1=Marchenko|first2=Anastasia S.|last2=Panova|first3=Natalia P.|last3=Kolosova|first4=Andrey S.|last4=Gudymo|first5=Svetlana V.|last5=Svyatchenko|first6=Alexey V.|last6=Danilenko|first7=Natalia N.|last7=Vasiltsova|first8=Marina L.|last8=Egorova|first9=Galina S.|last9=Onkhonova|first10=Pavel D.|last10=Zhestkov|first11=Nikolay G.|last11=Zinyakov|first12=Dmitriy B.|last12=Andreychuk|first13=Ilya A.|last13=Chvala|first14=Maksim N.|last14=Kosenko|first15=Anastasia A.|last15=Moiseeva|first16=Nikita D.|last16=Boldyrev|first17=Kiunnei N.|last17=Shadrinova|first18=Olga N.|last18=Perfilieva|first19=Alexander B.|last19=Ryzhikov|date=November 3, 2024|journal=Scientific Reports|volume=14|issue=1|pages=26490|doi=10.1038/s41598-024-78175-y|pmid=39489822 |pmc=11532466 |bibcode=2024NatSR..1426490M }} Host adaptation has been noted as being "rapid";{{Cite journal|title=Dynamic PB2-E627K substitution of influenza H7N9 virus indicates the in vivo genetic tuning and rapid host adaptation|first1=William J.|last1=Liu|first2=Jun|last2=Li|first3=Rongrong|last3=Zou|first4=Jingcao|last4=Pan|first5=Tao|last5=Jin|first6=Liqiang|last6=Li|first7=Peipei|last7=Liu|first8=Yingze|last8=Zhao|first9=Xinfen|last9=Yu|first10=Haoqiu|last10=Wang|first11=Guang|last11=Liu|first12=Hui|last12=Jiang|first13=Yuhai|last13=Bi|first14=Lei|last14=Liu|first15=Kwok-Yung|last15=Yuen|first16=Yingxia|last16=Liu|first17=George F.|last17=Gao|date=September 22, 2020|journal=Proceedings of the National Academy of Sciences|volume=117|issue=38|pages=23807–23814|doi=10.1073/pnas.2013267117|doi-access=free |pmid=32873642|pmc=7519270|bibcode=2020PNAS..11723807L }} the most recent outbreak was posited to be in San Bernardino County, California dairy cow herds in March 2025.{{Cite web|url=https://www.latimes.com/environment/story/2025-03-12/study-shows-widespread-h5n1-bird-flu-infection-in-cattle|title=Bird flu-infected San Bernardino County dairy cows may have concerning new mutation|date=March 12, 2025|website=Los Angeles Times}}

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