{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T18:38:43Z","timestamp":1792780723137,"version":"4.5.0"},"reference-count":63,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:00:00Z","timestamp":1792713600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Inserm","id":[{"id":"https:\/\/ror.org\/02vjkv261","id-type":"ROR","asserted-by":"crossref"}]},{"name":"CNRS"},{"name":"Universit\u00e9 Paris Cit\u00e9","id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"crossref"}]},{"name":"ANRS"},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CNRS, MITI interdisciplinary programs"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>As HIV-1 target cells, macrophages can be infected by cell-to-cell virus transfer from infected T cells through cell-cell fusion leading to the formation of virus-productive multinucleated giant cells (MGCs). We recently demonstrated that this route of infection escaped host cell restriction acting on the early steps of the viral life cycle. Here, we investigated whether restriction factors acting on late steps of HIV-1 replication were also bypassed in virus cell-to-cell infection of macrophages. We focused on the impact of the interferon(IFN)-induced factor BST-2\/tetherin acting on virus release, a process counteracted by the Vpu viral protein. We show that deletion of Vpu did not significantly affect HIV-1 cell-to-cell infection of IFN-stimulated macrophages, and virus assembly in virus containing compartments was not affected in MGCs. Accordingly, depletion of BST-2 in IFN-stimulated macrophages had no impact on virus cell-to-cell transfer, formation of MGCs and virus production. However, cell-to-cell infection of macrophages was still sensitive to the nelfinavir protease inhibitor, whereas we previously showed that this route of infection was resistant to antiviral drugs acting on early steps of virus replication. Our results show that HIV-1 cell-to-cell infection of macrophages escapes restriction factors acting on both early and late steps of the virus life cycle, but displays resistance to antiviral drugs specifically acting on the early steps of virus replication.<\/jats:p>","DOI":"10.1371\/journal.ppat.1014702","type":"journal-article","created":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T17:46:56Z","timestamp":1792777616000},"page":"e1014702","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["HIV-1 cell-to-cell infection of macrophages escapes restriction by the BST-2 host cell factor independently of the Vpu counteracting viral protein"],"prefix":"10.1371","volume":"22","author":[{"given":"Sen","family":"Yan","sequence":"first","affiliation":[{"name":"Institut Cochin, CNRS, Inserm, Universit\u00e9 Paris Cit\u00e9","place":["Paris, France"]},{"name":"NABI Laboratory, CNRS, Inserm, Universit\u00e9 Paris Cit\u00e9","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0610-5810","authenticated-orcid":true,"given":"Agathe","family":"Durringer","sequence":"additional","affiliation":[{"name":"Institut Cochin, CNRS, Inserm, Universit\u00e9 Paris Cit\u00e9","place":["Paris, France"]},{"name":"NABI Laboratory, CNRS, Inserm, Universit\u00e9 Paris Cit\u00e9","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Woottum","sequence":"additional","affiliation":[{"name":"Institut Cochin, CNRS, Inserm, Universit\u00e9 Paris Cit\u00e9","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3602-3530","authenticated-orcid":true,"given":"Serge","family":"Benichou","sequence":"additional","affiliation":[{"name":"Institut Cochin, CNRS, Inserm, Universit\u00e9 Paris Cit\u00e9","place":["Paris, 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Woottum","year":"2024","journal-title":"Viruses"},{"issue":"9","key":"ppat.1014702.ref007","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.3390\/v16091484","article-title":"New Therapies and Strategies to Curb HIV Infections with a Focus on Macrophages and Reservoirs","volume":"16","author":"M Marra","year":"2024","journal-title":"Viruses"},{"issue":"5","key":"ppat.1014702.ref008","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/s41564-023-01349-3","article-title":"Monocyte-derived macrophages contain persistent latent HIV reservoirs","volume":"8","author":"RT Veenhuis","year":"2023","journal-title":"Nat Microbiol"},{"issue":"6","key":"ppat.1014702.ref009","doi-asserted-by":"crossref","first-page":"611","DOI":"10.3390\/pathogens11060611","article-title":"HIV Latency in Myeloid Cells: Challenges for a Cure","volume":"11","author":"A Chitrakar","year":"2022","journal-title":"Pathogens"},{"issue":"2","key":"ppat.1014702.ref010","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s13365-018-0631-7","article-title":"Optimizing animal models for HIV-associated CNS dysfunction and CNS reservoir research","volume":"24","author":"J Joseph","year":"2018","journal-title":"J Neurovirol"},{"issue":"1","key":"ppat.1014702.ref011","doi-asserted-by":"crossref","first-page":"3890","DOI":"10.1038\/s41598-021-82066-x","article-title":"T cell-tropic HIV efficiently infects alveolar macrophages through contact with infected CD4+\u2009T cells","volume":"11","author":"AE Schiff","year":"2021","journal-title":"Sci Rep"},{"key":"ppat.1014702.ref012","doi-asserted-by":"crossref","first-page":"1694065","DOI":"10.3389\/fimmu.2025.1694065","article-title":"Inflammatory and redox reprogramming of macrophages by HIV cell-to-cell transmission inhibits bone resorption capacity","volume":"16","author":"FA 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