{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:50:32Z","timestamp":1790783432764,"version":"4.1.0"},"reference-count":111,"publisher":"Oxford University Press (OUP)","issue":"16","license":[{"start":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T00:00:00Z","timestamp":1661126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FluCode Project","award":["ProjetANR-19-CE11-0027"],"award-info":[{"award-number":["ProjetANR-19-CE11-0027"]}]},{"DOI":"10.13039\/501100001665","name":"French National Research Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Marie Sk\u0142odowska-Curie Actions Innovative Training Networks","award":["955974"],"award-info":[{"award-number":["955974"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The genome of influenza A virus (IAV) consists of eight unique viral RNA segments. This genome organization allows genetic reassortment between co-infecting IAV strains, whereby new IAVs with altered genome segment compositions emerge. While it is known that reassortment events can create pandemic IAVs, it remains impossible to anticipate reassortment outcomes with pandemic prospects. Recent research indicates that reassortment is promoted by a viral genome packaging mechanism that delivers the eight genome segments as a supramolecular complex into the virus particle. This finding holds promise of predicting pandemic IAVs by understanding the intermolecular interactions governing this genome packaging mechanism. Here, we critically review the prevailing mechanistic model postulating that IAV genome packaging is orchestrated by a network of intersegmental RNA\u2013RNA interactions. Although we find supporting evidence, including segment-specific packaging signals and experimentally proposed RNA\u2013RNA interaction networks, this mechanistic model remains debatable due to a current shortage of functionally validated intersegmental RNA\u2013RNA interactions. We speculate that identifying such functional intersegmental RNA\u2013RNA contacts might be hampered by limitations of the utilized probing techniques and the inherent complexity of the genome packaging mechanism. Nevertheless, we anticipate that improved probing strategies combined with a mutagenesis-based validation could facilitate their discovery.<\/jats:p>","DOI":"10.1093\/nar\/gkac688","type":"journal-article","created":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T09:37:35Z","timestamp":1661161055000},"page":"9023-9038","source":"Crossref","is-referenced-by-count":29,"title":["The influenza A virus genome packaging network \u2014 complex, flexible and yet unsolved"],"prefix":"10.1093","volume":"50","author":[{"given":"Celia","family":"Jakob","sequence":"first","affiliation":[{"name":"Institute of Virology, Medical Center \u2013 University of Freiburg , 79104 Freiburg , Germany"},{"name":"Faculty of Medicine, University of Freiburg , 79110 Freiburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rithu","family":"Paul-Stansilaus","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, CNRS, Architecture et R\u00e9activit\u00e9 de l'ARN , UPR 9002, IBMC, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2972-6855","authenticated-orcid":false,"given":"Martin","family":"Schwemmle","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical Center \u2013 University of Freiburg , 79104 Freiburg , Germany"},{"name":"Faculty of Medicine, University of Freiburg , 79110 Freiburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4209-3976","authenticated-orcid":false,"given":"Roland","family":"Marquet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, CNRS, Architecture et R\u00e9activit\u00e9 de l'ARN , UPR 9002, IBMC, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hardin","family":"Bolte","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical Center \u2013 University of Freiburg , 79104 Freiburg , Germany"},{"name":"Faculty of Medicine, University of Freiburg , 79110 Freiburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,22]]},"reference":[{"key":"2022090900001109500_B1","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.chom.2010.05.009","article-title":"Influenza virus evolution, host adaptation, and pandemic formation","volume":"7","author":"Taubenberger","year":"2010","journal-title":"Cell Host Microbe"},{"key":"2022090900001109500_B2","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.3390\/v13112250","article-title":"Influenza A viruses and zoonotic events-are we creating our own reservoirs?","volume":"13","author":"Kessler","year":"2021","journal-title":"Viruses"},{"key":"2022090900001109500_B3","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/nature08182","article-title":"Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic","volume":"459","author":"Smith","year":"2009","journal-title":"Nature"},{"key":"2022090900001109500_B4","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1093\/infdis\/jiv534","article-title":"Global mortality impact of the 1957\u20131959 influenza pandemic","volume":"213","author":"Viboud","year":"2016","journal-title":"J. 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