{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:51:19Z","timestamp":1790718679154,"version":"4.1.0"},"reference-count":82,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T00:00:00Z","timestamp":1640217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The Flavivirus genus includes a number of important viruses that are pathogenic to humans and animals and are responsible for outbreaks across the globe. Integrins, a family of heterodimeric transmembrane molecules expressed in all nucleated cells mediate critical functions of cell physiology and cell cycle. Integrins were previously postulated to be involved in flavivirus entry and to modulate flavivirus replication efficiency. In the present study, mouse embryonic fibroblasts (MEF), lacking the expression of \u03b1V\u03b23 integrin (MEF-\u03b1V\u03b23\u2212\/\u2212), were infected with four different flaviviruses, namely yellow fever virus (YFV), West Nile virus (WNV), Usutu virus (USUV) and Langat virus (LGTV). The effects of the \u03b1V\u03b23 integrin absence in double-knockout MEF-\u03b1V\u03b23\u2212\/\u2212 on flavivirus binding, internalization and replication were compared to the respective wild-type cells. Binding to the cell surface for all four flaviviruses was not affected by the ablation of \u03b1V\u03b23 integrin, whereas internalization of USUV and WNV was slightly affected by the loss of \u03b1V\u03b23 integrin expression. Most interestingly, the deletion of \u03b1V\u03b23 integrin strongly impaired replication of all flaviviruses with a reduction of up to 99% on virus yields and a strong reduction on flavivirus anti-genome RNA synthesis. In conclusion, our results demonstrate that \u03b1V\u03b23 integrin expression in flavivirus-susceptible cell lines enhances the flavivirus replication.<\/jats:p>","DOI":"10.3390\/v14010018","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T02:02:57Z","timestamp":1640224977000},"page":"18","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["\u03b1V\u03b23 Integrin Expression Is Essential for Replication of Mosquito and Tick-Borne Flaviviruses in Murine Fibroblast Cells"],"prefix":"10.3390","volume":"14","author":[{"given":"Vinicius Pinho dos","family":"Reis","sequence":"first","affiliation":[{"name":"Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, S\u00fcdufer 10, 17493 Greifswald-Insel Riems, Germany"},{"name":"Institute for Virology, Philipps University Marburg, Hans-Meerwein-Stra\u00dfe 2, 35043 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3229-8377","authenticated-orcid":false,"given":"Markus","family":"Keller","sequence":"additional","affiliation":[{"name":"Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, S\u00fcdufer 10, 17493 Greifswald-Insel Riems, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4828-7974","authenticated-orcid":false,"given":"Katja","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Microbiological Diagnostics, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5620-1528","authenticated-orcid":false,"given":"Rainer G\u00fcnter","family":"Ulrich","sequence":"additional","affiliation":[{"name":"Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, S\u00fcdufer 10, 17493 Greifswald-Insel Riems, Germany"},{"name":"Deutsches Zentrum f\u00fcr Infektionsforschung(DZIF), Partner Site Hamburg-L\u00fcbeck-Borstel-Riems, S\u00fcdufer 10, 17493 Greifswald-Insel Riems, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0215-185X","authenticated-orcid":false,"given":"Martin Hermann","family":"Groschup","sequence":"additional","affiliation":[{"name":"Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, S\u00fcdufer 10, 17493 Greifswald-Insel Riems, Germany"},{"name":"Deutsches Zentrum f\u00fcr Infektionsforschung(DZIF), Partner Site Hamburg-L\u00fcbeck-Borstel-Riems, S\u00fcdufer 10, 17493 Greifswald-Insel Riems, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/s41564-020-0714-0","article-title":"The continued threat of emerging flaviviruses","volume":"5","author":"Pierson","year":"2020","journal-title":"Nat. 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