Journal article
T cell-tropic HIV efficiently infects alveolar macrophages through contact with infected CD4+T cells
Scientific reports, Vol.11(1), pp.3890-3890
02/16/2021
DOI: 10.1038/s41598-021-82066-x
PMCID: PMC7886866
PMID: 33594125
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.
Details
- Title: Subtitle
- T cell-tropic HIV efficiently infects alveolar macrophages through contact with infected CD4+T cells
- Creators
- Abigail E. Schiff - Ragon Institute of MGH, MIT and HarvardAlice H. Linder - Ragon Institute of MGH, MIT and HarvardShillah N. Luhembo - Ragon Institute of MGH, MIT and HarvardStephanie Banning - Brigham and Women's HospitalMartin J. Deymier - Ragon Institute of MGH, MIT and HarvardThomas J. Diefenbach - Ragon Institute of MGH, MIT and HarvardAmy K. Dickey - Massachusetts General HospitalAthe M. Tsibris - Brigham and Women's HospitalAlejandro B. Balazs - Ragon Institute of MGH, MIT and HarvardJosalyn L. Cho - Massachusetts General HospitalBenjamin D. Medoff - Massachusetts General HospitalGerhard Walzl - South African Medical Research CouncilRobert J. Wilkinson - Imperial College LondonWendy A. Burgers - Wellcome Centre for Infectious Diseases Research in AfricaBjoern Corleis - Harvard Medical SchoolDouglas S. Kwon - Harvard University
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.11(1), pp.3890-3890
- DOI
- 10.1038/s41598-021-82066-x
- PMID
- 33594125
- PMCID
- PMC7886866
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Publisher
- NATURE PORTFOLIO
- Number of pages
- 14
- Grant note
- T32GM007753 / National Institute of General Medical Sciences; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) FC0010218 / Francis Crick Institute from Wellcome TMA2016SF-1535 / EDCTP2 program - European Union (EU)'s Horizon 2020 program SATBBI grant Charles H. Hood Foundation FC0010218 / Cancer Research UK 96841; 86535 / South African National Research Foundation; National Research Foundation - South Africa FC0010218 / UK Research and Innovation; UK Research & Innovation (UKRI) Gilead Sciences Research Scholars Program in HIV MGH Transformative Scholars Program U01HL121827; F30HL134566-02 / National Institutes of Health Grant from the National Heart, Lung and Blood Institute FP7-Health-F3-2012-305578 / European Union; European Commission 203135; FC0010218 / Wellcome DP2DA040254 / National Institute on Drug Abuse (NIDA) Avenir New Innovator Award Strategic Health Innovation Partnership, SAMRC R01AI108538 / National Institute of Allergy and Infectious Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) Burroughs Wellcome Fund 089832/Z/09/Z; 203135; 104803 / Wellcome Trust
- Language
- English
- Date published
- 02/16/2021
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984359924002771
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