{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:42:05Z","timestamp":1791258125475,"version":"4.1.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T00:00:00Z","timestamp":1714953600000},"content-version":"vor","delay-in-days":126,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Nih","award":["DP2 AI175474 R01 AI170520"],"award-info":[{"award-number":["DP2 AI175474 R01 AI170520"]}]},{"name":"Nih","award":["DP2 AI175474 R01 AI170520"],"award-info":[{"award-number":["DP2 AI175474 R01 AI170520"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Since the influenza pandemic in 1968, influenza A(H3N2) viruses have become endemic. In this state, H3N2 viruses continuously evolve to overcome immune pressure as a result of prior infection or vaccination, as is evident from the accumulation of mutations in the surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). However, phylogenetic studies have also demonstrated ongoing evolution in the influenza A(H3N2) virus RNA polymerase complex genes. The RNA polymerase complex of seasonal influenza A(H3N2) viruses produces mRNA for viral protein synthesis and replicates the negative sense viral RNA genome (vRNA) through a positive sense complementary RNA intermediate (cRNA). Presently, the consequences and selection pressures driving the evolution of the polymerase complex remain largely unknown. Here, we characterize the RNA polymerase complex of seasonal influenza A(H3N2) viruses representative of nearly 50\u2009years of influenza A(H3N2) virus evolution. The H3N2 polymerase complex is a reassortment of human and avian influenza virus genes. We show that since 1968, influenza A(H3N2) viruses have increased the transcriptional activity of the polymerase complex while retaining a close balance between mRNA, vRNA, and cRNA levels. Interestingly, the increased polymerase complex activity did not result in increased replicative ability on differentiated human airway epithelial (HAE) cells. We hypothesize that the evolutionary increase in polymerase complex activity of influenza A(H3N2) viruses may compensate for the reduced HA receptor binding and avidity that is the result of the antigenic evolution of influenza A(H3N2) viruses.<\/jats:p>","DOI":"10.1093\/ve\/veae030","type":"journal-article","created":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T05:06:20Z","timestamp":1714971980000},"source":"Crossref","is-referenced-by-count":9,"title":["Long-term evolution of human seasonal influenza virus A(H3N2) is associated with an increase in polymerase complex activity"],"prefix":"10.1093","volume":"10","author":[{"given":"Ren\u00e9 M","family":"Vigeveno","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Amsterdam UMC , Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvin X","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Amsterdam UMC , Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1586-4464","authenticated-orcid":false,"given":"Robert P","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edyth","family":"Parker","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Amsterdam UMC , Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"de Haan","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Amsterdam UMC , Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"van Leeuwen","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Amsterdam UMC , Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katina D","family":"Hulme","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Amsterdam UMC , Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2906-8335","authenticated-orcid":false,"given":"Adam S","family":"Lauring","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and Division of Infectious Diseases, Department of Internal Medicine, University of Michigan , 1150 W. Medical Center Dr., Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5129-3953","authenticated-orcid":false,"given":"Aartjan J W","family":"te Velthuis","sequence":"additional","affiliation":[{"name":"Lewis Thomas Laboratory, Department of Molecular Biology, Princeton University , Washington Road, Princeton, NJ 08544, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert-Jan","family":"Boons","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Utrecht, The Netherlands"},{"name":"Complex Carbohydrate Research Center, University of Georgia , 315 Riverbend Road, Athens, GA 30602, USA"},{"name":"Bijvoet Center for Biomolecular Research, Utrecht University , Padualaan 8, Utrecht 3584 CH, The Netherlands"},{"name":"Department of Chemistry, University of Georgia , 315 Riverbend Rd, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron A M","family":"Fouchier","sequence":"additional","affiliation":[{"name":"Department of Viroscience, Erasmus MC , Dr. Molewaterplein 50, Rotterdam 3015 GE, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2113-162X","authenticated-orcid":false,"given":"Colin A","family":"Russell","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Amsterdam UMC , Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menno D","family":"de Jong","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Amsterdam UMC , Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4248-6008","authenticated-orcid":false,"given":"Dirk","family":"Eggink","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Amsterdam UMC , Amsterdam, The Netherlands"},{"name":"Center for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM) , Antonie van Leeuwenhoeklaan 9, Bilthoven 3721 MA, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,4]]},"reference":[{"key":"2024052809190787400_R1","doi-asserted-by":"crossref","first-page":"9605","DOI":"10.1128\/JVI.78.18.9605-9611.2004","article-title":"Effect of the Addition of Oligosaccharides on the Biological Activities and Antigenicity of Influenza A\/H3N2 Virus Hemagglutinin","volume":"78","author":"Abe","year":"2004","journal-title":"Journal of 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