T cell‑tropic HIV efciently infects alveolar macrophages through contact with infected CD4+T cells

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dc.contributor.authorSchiff, Abigail E.en_ZA
dc.contributor.authorLinder, Alice H.en_ZA
dc.contributor.authorLuhembo, Shillah N.en_ZA
dc.contributor.authorBanning, Stephanieen_ZA
dc.contributor.authorDeymier, Martin J.en_ZA
dc.contributor.authorDiefenbach, Thomas J.en_ZA
dc.contributor.authorDickey, Amy K.en_ZA
dc.contributor.authorTsibris, Athe M.en_ZA
dc.contributor.authorBalazs, Alejandro B.en_ZA
dc.contributor.authorCho, Josalyn L.en_ZA
dc.contributor.authorMedoff, Benjamin D.en_ZA
dc.contributor.authorWalzl, Gerharden_ZA
dc.contributor.authorWilkinson, Robert J.en_ZA
dc.contributor.authorBurgers, Wendy A.en_ZA
dc.contributor.authorCorleis, Bjornen_ZA
dc.contributor.authorKwon, Douglas S.en_ZA
dc.date.accessioned2023-04-03T12:42:30Zen_ZA
dc.date.available2023-04-03T12:42:30Zen_ZA
dc.date.issued2021-02en_ZA
dc.descriptionCITATION: Schiff, A. E. et al. 2021. T cell‑tropic HIV efciently infects alveolar macrophages through contact with infected CD4+T cells. Scientific Reports, 11:3890, doi:10.1038/s41598-021-82066-x.en_ZA
dc.descriptionThe original publication is available at https://www.nature.comen_ZA
dc.description.abstractAlveolar macrophages (AMs) are critical for defense against airborne pathogens and AM dysfunction is thought to contribute to the increased burden of pulmonary infections observed in individuals living with HIV-1 (HIV). While HIV nucleic acids have been detected in AMs early in infection, circulating HIV during acute and chronic infection is usually CCR5 T cell-tropic (T-tropic) and enters macrophages inefficiently in vitro. The mechanism by which T-tropic viruses infect AMs remains unknown. We collected AMs by bronchoscopy performed in HIV-infected, antiretroviral therapy (ART)-naive and uninfected subjects. We found that viral constructs made with primary HIV envelope sequences isolated from both AMs and plasma were T-tropic and inefficiently infected macrophages. However, these isolates productively infected macrophages when co-cultured with HIV-infected CD4+ T cells. In addition, we provide evidence that T-tropic HIV is transmitted from infected CD4+ T cells to the AM cytosol. We conclude that AM-derived HIV isolates are T-tropic and can enter macrophages through contact with an infected CD4+ T cell, which results in productive infection of AMs. CD4+ T cell-dependent entry of HIV into AMs helps explain the presence of HIV in AMs despite inefficient cell-free infection, and may contribute to AM dysfunction in people living with HIV.en_ZA
dc.description.urihttps://www.nature.com/articles/s41598-021-82066-xen_ZA
dc.description.versionPublisher's versionen_ZA
dc.format.extent14 pagesen_ZA
dc.identifier.citationSchiff, A. E. et al. 2021. T cell‑tropic HIV efciently infects alveolar macrophages through contact with infected CD4+T cells. Scientific Reports, 11:3890, doi:10.1038/s41598-021-82066-x.en_ZA
dc.identifier.issn2045-2322 (online)en_ZA
dc.identifier.otherdoi:10.1038/s41598-021-82066-xen_ZA
dc.identifier.urihttp://hdl.handle.net/10019.1/126760en_ZA
dc.language.isoen_ZAen_ZA
dc.publisherNatureen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectLungs -- Diseasesen_ZA
dc.subjectMacrophagesen_ZA
dc.subjectAlveolitisen_ZA
dc.subjectT cellsen_ZA
dc.subjectHIV infectionsen_ZA
dc.titleT cell‑tropic HIV efciently infects alveolar macrophages through contact with infected CD4+T cellsen_ZA
dc.typeArticleen_ZA
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