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In this study, we utilized the Sindbis virus (SINV), a model alphavirus, to investigate the infection processes in mosquito and mammalian cells. One member of the Flotillin family of lipid\u2010raft protein from\n                    <jats:italic>Culex quinquefasciatus<\/jats:italic>\n                    , CqFlotillin 2, was found to bind SINV glycoprotein E2 and to facilitate SINV infection in\n                    <jats:italic>C. quinquefasciatus<\/jats:italic>\n                    cell line and live mosquitoes, as well as facilitating viral transmission to mice via mosquito vectors. Notably, instead of affecting viral attachment to cell surface, entry into cells, or replication, CqFlotillin 2 facilitates viral release from cells and intercellular spread, which positively correlates to the formation of filopodial extension. This function is conserved among Flotillin 2 homologs in promoting SINV infection in various mosquito and mammal host cells. Furthermore, Flotillin 2 promotes the infection of another alphavirus, Semliki Forest virus (SFV), in mosquito and mammalian cells by facilitating viral release from cells. This work suggests Flotillin 2 as a potential cellular co\u2010factor implicated in alphavirus release and highlights\n                    <jats:italic>Flotillin 2<\/jats:italic>\n                    as a promising target for controlling alphavirus infection and transmission.\n                  <\/jats:p>","DOI":"10.1111\/1744-7917.70361","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T07:15:46Z","timestamp":1789629346000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lipid raft protein Flotillin 2 facilitates alphavirus infection through promoting viral release"],"prefix":"10.1111","author":[{"given":"Tianyu","family":"Guan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology Chinese Academy of Sciences  Beijing China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology Chinese Academy of Sciences  Beijing China"},{"name":"College of Life Sciences Hebei University  Baoding Hebei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyu","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology Chinese Academy of Sciences  Beijing China"},{"name":"College of Life Sciences Hebei University  Baoding Hebei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology Chinese Academy of Sciences  Beijing China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liya","family":"Wei","sequence":"additional","affiliation":[{"name":"College of Life Sciences Hebei University  Baoding Hebei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology Chinese Academy of Sciences  Beijing China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6215-7159","authenticated-orcid":false,"given":"Feng","family":"Cui","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology Chinese Academy of Sciences  Beijing China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/rmv.1876","article-title":"Sindbis virus as a human pathogen\u2010epidemiology, clinical picture and pathogenesis: Sindbis virus as a human pathogen","volume":"26","author":"Adouchief S.","year":"2016","journal-title":"Reviews in Medical Virology"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/boc.202400134"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/v10020089"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12028-017-0413-8"},{"key":"e_1_2_8_6_1","doi-asserted-by":"crossref","DOI":"10.1093\/jtm\/taae123","article-title":"From bench to clinic: the development of VLA1553\/IXCHIQ, a live\u2010attenuated chikungunya vaccine","volume":"31","author":"Chen L.H.","year":"2024","journal-title":"Journal of Travel Medicine"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04326-0"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-virology-031413-085513"},{"key":"e_1_2_8_9_1","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2409334121","article-title":"Structure of the flotillin complex in a native membrane environment","volume":"121","author":"Fu Z.","year":"2024","journal-title":"Proceedings of the National Academy of Sciences USA"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/pbi.14274"},{"key":"e_1_2_8_11_1","first-page":"1859","article-title":"Rapid epidemic expansion of Chikungunya virus East\/Central\/South African lineage","volume":"29","author":"Giovanetti M.","year":"2023","journal-title":"Paraguay. 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