s41598-021-82066-x.pdf (2.46 MB)
Download fileT cell-tropic HIV efficiently infects alveolar macrophages through contact with infected CD4+ T cells.
journal contribution
posted on 2021-03-03, 13:06 authored by Abigail E Schiff, Alice H Linder, Shillah N Luhembo, Stephanie Banning, Martin J Deymier, Thomas J Diefenbach, Amy K Dickey, Athe M Tsibris, Alejandro B Balazs, Josalyn L Cho, Benjamin D Medoff, Gerhard Walzl, Robert J Wilkinson, Wendy A Burgers, Björn Corleis, Douglas S KwonAlveolar 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.