Author:
Schiff Abigail E.,Linder Alice H.,Luhembo Shillah N.,Banning Stephanie,Deymier Martin J.,Diefenbach Thomas J.,Dickey Amy K.,Tsibris Athe M.,Balazs Alejandro B.,Cho Josalyn L.,Medoff Benjamin D.,Walzl Gerhard,Wilkinson Robert J.,Burgers Wendy A.,Corleis Björn,Kwon Douglas S.
Abstract
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.
Funder
National Heart, Lung, and Blood Institute
National Institute of General Medical Sciences
National Institute on Drug Abuse
MGH Transformative Scholars Program
Charles H. Hood Foundation
Gilead Sciences
National Institute of Allergy and Infectious Diseases
South African National Research Foundation
South African Tuberculosis Bioinformatics Institute
Wellcome Trust
Cancer Research UK
UK Research and Innovation
European Union
Strategic Health Innovation Partnership
Horizon 2020 Framework Programme
Burroughs Wellcome Fund
Publisher
Springer Science and Business Media LLC
Cited by
18 articles.
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