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However, the underlying mechanism is not fully understood. Here, we report that M-Sec promotes the production of infectious HIV-1 virus. The major viral structural protein Gag distributed as many puncta in infected cells, which is one of the indicators of viral particle formation. The knockdown of M-Sec hindered the Gag puncta formation and co-localization of Gag with the viral envelope protein Env in cells, and reduced the amount of Env and infectivity of the produced virus. Consistent with these results, the over-expression of M-Sec induced the accumulation of Gag puncta, Gag\/Env co-localization, and Env incorporation into virus and viral infectivity. M-Sec is known to bind phosphatidylinositol 4,5-bisphosphate (PIP2) and a small GTPase Ral, both of which were required for the M-Sec-mediated HIV-1 regulation. The exocyst complex, which is the downstream effector of Ral, was also required for the M-Sec-mediated HIV-1 regulation. Because PIP2, Ral and the exocyst complex are important for the M-Sec-mediated formation of the long plasma membrane protrusions, the present study suggests that M-Sec promotes HIV-1 transmission by acting on both cell structures and viral production through these overlapping components.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013717","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:55:53Z","timestamp":1780336553000},"page":"e1013717","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["M-Sec promotes the production of infectious HIV-1 virus through the exocyst complex in macrophages"],"prefix":"10.1371","volume":"22","author":[{"given":"Reem 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