{ "abstract": "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. Author summary: Macrophages participate in HIV-1 dissemination, as well as in the establishment of the tissue virus-reservoirs. The work reported here show that HIV-1 cell-to-cell infection of macrophages from infected T cells, escapes restriction by the interferon-stimulated BST-2 protein acting in the last step of virus release. We demonstrate that this mechanism is independent of expression of the Vpu counteracting viral protein. However, in contrast to the resistance previously observed to antiviral drugs acting on early steps of virus replication, cell-to-cell HIV-1 spreading in macrophages remained sensitive to the nelfinavir protease antiretroviral inhibitor acting on virus maturation. These results contribute to a better understanding of HIV-1 persistence and evasion to host innate immune response in people living with HIV.", "abstract_shown": true, "affiliations": [ "Institut Cochin, CNRS, Inserm, Université Paris Cité, Paris, France", "NABI Laboratory, CNRS, Inserm, Université Paris Cité, Paris, France" ], "article_type": "Research Article", "arxiv": null, "author_total": 4, "authors": [ { "affs": [ 0 ], "name": "Sen Yan" }, { "affs": [ 1 ], "name": "Agathe Durringer" }, { "name": "Marie Woottum" }, { "name": "Serge Benichou" } ], "bibtex": "https://research.draconitic.com/paper/7cr8fkhsxr4gg.bib", "cited_by": 0, "doi": "10.1371/journal.ppat.1014702", "fulltext_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014702", "id": "7cr8fkhsxr4gg", "issns": [ "1553-7374" ], "landing_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014702", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2406|HIV Research and Treatment" ], [ "plos", "/Biology and life sciences/Cell biology/Cell physiology/Cell fusion" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Blood cells/White blood cells/Macrophages" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Blood cells/White blood cells/T helper cells" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells/White blood cells/Macrophages" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells/White blood cells/T helper cells" ], [ "plos", "/Biology and life sciences/Immunology/Immune cells/White blood cells/Macrophages" ], [ "plos", "/Biology and life sciences/Immunology/Immune cells/White blood cells/T helper cells" ], [ "plos", "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Viral pathogens/Immunodeficiency viruses/HIV/HIV-1" ], [ "plos", "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Viral pathogens/Retroviruses/Lentivirus/HIV/HIV-1" ], [ "plos", "/Biology and life sciences/Microbiology/Virology/Viral replication" ], [ "plos", "/Biology and life sciences/Molecular biology/Molecular biology techniques/Transfection" ], [ "plos", "/Biology and life sciences/Organisms/Viruses/Immunodeficiency viruses/HIV/HIV-1" ], [ "plos", "/Biology and life sciences/Organisms/Viruses/RNA viruses/Retroviruses/Lentivirus/HIV/HIV-1" ], [ "plos", "/Biology and life sciences/Organisms/Viruses/Viral pathogens/Immunodeficiency viruses/HIV/HIV-1" ], [ "plos", "/Biology and life sciences/Organisms/Viruses/Viral pathogens/Retroviruses/Lentivirus/HIV/HIV-1" ], [ "plos", "/Medicine and health sciences/Immunology/Immune cells/White blood cells/Macrophages" ], [ "plos", "/Medicine and health sciences/Immunology/Immune cells/White blood cells/T helper cells" ], [ "plos", "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Viral pathogens/Immunodeficiency viruses/HIV/HIV-1" ], [ "plos", "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Viral pathogens/Retroviruses/Lentivirus/HIV/HIV-1" ], [ "plos", "/Research and analysis methods/Molecular biology techniques/Transfection" ], [ "plos", "/Research and analysis methods/Specimen preparation and treatment/Staining/Cell staining" ], [ "plos", "/Research and analysis methods/Spectrum analysis techniques/Spectrophotometry/Cytophotometry/Flow cytometry" ] ], "openalex": "W7223302825", "pdf_url": "https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1014702&type=printable", "pmcid": null, "pmid": null, "published": "2026-10-23", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/7cr8fkhsxr4gg.ris", "sources": [ { "first_seen": "2026-10-30T12:17:17Z", "native_id": "10.1371/journal.ppat.1014702", "source": "plos", "url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014702" } ], "subjects": [ { "field": "biology", "origin": "plos:cell biology", "subfield": "cell-biology" }, { "field": "biology", "origin": "plos:immunology", "subfield": "immunology" }, { "field": "biology", "origin": "plos:microbiology", "subfield": "microbiology" } ], "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", "title_text": "HIV-1 cell-to-cell infection of macrophages escapes restriction by the BST-2 host cell factor independently of the Vpu counteracting viral protein", "type": "peer-reviewed", "updated_at": "2026-10-30T12:17:17Z", "url": "https://research.draconitic.com/paper/7cr8fkhsxr4gg", "venue": "PLOS Pathogens", "versions": [] }