{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:55:36Z","timestamp":1778028936371,"version":"3.51.4"},"reference-count":55,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"16","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,4,18]]},"abstract":"<jats:p>\n            HIV-1 Nef enhances virus propagation by down-regulating CD4 and SERINC5. However, recent evidence points to the existence of an additional Nef-sensitive restriction mechanism. We now show that Nef suppresses the aberrant cleavage of HIV-1 gp41 by ADAM10, a virion-associated cellular ectodomain sheddase, and thus increases the amount of HIV-1 envelope glycoprotein (Env) on virions. Additionally, Nef inhibits the shedding of at least some cellular ADAM10 substrates, resulting in their accumulation on HIV-1 virions. Whereas Nef\n            <jats:sup>+<\/jats:sup>\n            HIV-1 replicated only marginally better in the absence of ADAM10, the propagation of Nef\n            <jats:sup>\u2212<\/jats:sup>\n            HIV-1 was notably rescued in ADAM10\n            <jats:sup>\u2212<\/jats:sup>\n            T cell lines. Crucially, Nef\n            <jats:sup>\u2212<\/jats:sup>\n            HIV-1 also benefited from the absence of ADAM10 in primary CD4\n            <jats:sup>+<\/jats:sup>\n            T cells. Collectively, our results indicate that ADAM10 negatively affects both laboratory-adapted and primary HIV-1 strains by shedding the ectodomains of viral and cellular transmembrane proteins from virions and that Nef rescues virus replication by counteracting ADAM10.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adt1836","type":"journal-article","created":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T17:58:46Z","timestamp":1744999126000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":2,"title":["The ectodomain sheddase ADAM10 restricts HIV-1 propagation and is counteracted by Nef"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7999-4578","authenticated-orcid":true,"given":"Balaji","family":"Olety","sequence":"first","affiliation":[{"name":"Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, 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