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Here, we provide evidence that cellular protein M-Sec plays a critical role in this process. When purified and briefly cultured, CD4<jats:sup>+<\/jats:sup> T cells of HTLV-1 carriers, but not of HTLV-1<jats:sup>-<\/jats:sup> individuals, expressed M-Sec. The viral protein Tax was revealed to mediate M-Sec induction. Knockdown or pharmacological inhibition of M-Sec reduced viral infection in multiple co-culture conditions. Furthermore, M-Sec knockdown reduced the number of proviral copies in the tissues of a mouse model of HTLV-1 infection. Phenotypically, M-Sec knockdown or inhibition reduced not only plasma membrane protrusions and migratory activity of cells, but also large clusters of Gag, a viral structural protein required for the formation of viral particles. Taken together, these results suggest that M-Sec induced by Tax mediates an efficient cell-to-cell viral infection, which is likely due to enhanced membrane protrusions, cell migration, and the clustering of Gag.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010126","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T19:00:40Z","timestamp":1638212440000},"page":"e1010126","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["M-Sec induced by HTLV-1 mediates an efficient viral transmission"],"prefix":"10.1371","volume":"17","author":[{"given":"Masateru","family":"Hiyoshi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naofumi","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youssef M.","family":"Eltalkhawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Noyori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameh","family":"Lotfi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9198-2980","authenticated-orcid":true,"given":"Jutatip","family":"Panaampon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3124-5206","authenticated-orcid":true,"given":"Seiji","family":"Okada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuetsu","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4746-2726","authenticated-orcid":true,"given":"Takaharu","family":"Ueno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0775-5580","authenticated-orcid":true,"given":"Jun-ichi","family":"Fujisawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3820-9542","authenticated-orcid":true,"given":"Tadaki","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Hasegawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1296-9006","authenticated-orcid":true,"given":"Masahito","family":"Tokunaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1495-7810","authenticated-orcid":true,"given":"Yorifumi","family":"Satou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-ichirou","family":"Yasunaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0473-754X","authenticated-orcid":true,"given":"Masao","family":"Matsuoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8843-406X","authenticated-orcid":true,"given":"Atae","family":"Utsunomiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2531-4770","authenticated-orcid":true,"given":"Shinya","family":"Suzu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,11,29]]},"reference":[{"key":"ppat.1010126.ref001","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1126\/science.1093133","article-title":"Nanotubular highways for intercellular organelle transport","volume":"303","author":"A Rustom","year":"2004","journal-title":"Science"},{"key":"ppat.1010126.ref002","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ceb.2021.03.003","article-title":"Tunneling nanotubes: reshaping connectivity","volume":"71","author":"C. 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