T cell‑tropic HIV efciently infects alveolar macrophages through contact with infected CD4+T cells
Date
2021-02
Journal Title
Journal ISSN
Volume Title
Publisher
Nature
Abstract
Alveolar 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.
Description
CITATION: 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.
The original publication is available at https://www.nature.com
The original publication is available at https://www.nature.com
Keywords
Lungs -- Diseases, Macrophages, Alveolitis, T cells, HIV infections
Citation
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.