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T cell-tropic HIV efficiently infects alveolar macrophages through contact with infected CD4+ T cells

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Title: T cell-tropic HIV efficiently infects alveolar macrophages through contact with infected CD4+ T cells
Authors: Schiff, AE
Linder, AH
Luhembo, SN
Banning, S
Deymier, MJ
Diefenbach, TJ
Dickey, AK
Tsibris, AM
Balazs, AB
Cho, J
Medoff, B
Walzl, G
Wilkinson, RJ
Burgers, WA
Corleis, B
Kwon, DS
Item Type: Journal Article
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.
Issue Date: 16-Feb-2021
Date of Acceptance: 8-Dec-2020
URI: http://hdl.handle.net/10044/1/85029
DOI: 10.1038/s41598-021-82066-x
ISSN: 2045-2322
Publisher: Nature Publishing Group
Journal / Book Title: Scientific Reports
Volume: 11
Copyright Statement: © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Sponsor/Funder: Wellcome Trust
Wellcome Trust
Funder's Grant Number: 104803/Z/14/Z
Publication Status: Published
Article Number: ARTN 3890
Appears in Collections:Department of Infectious Diseases
Faculty of Medicine

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