Near full-length HIV sequencing in multiple tissues collected postmortem reveals shared clonal expansions across distinct reservoirs during ART
Caroline Dufour,
Maria Julia Ruiz,
Amélie Pagliuzza,
Corentin Richard,
Aniqa Shahid,
Rémi Fromentin,
Rosalie Ponte,
Amélie Cattin,
Tomas Raul Wiche Salinas,
Syim Salahuddin,
Teslin Sandstrom,
Stephanie Burke Schinkel,
Cecilia T. Costiniuk,
Mohammad-Ali Jenabian,
Petronela Ancuta,
Jean-Pierre Routy,
Éric A. Cohen,
Zabrina L. Brumme,
Christopher Power,
Jonathan B. Angel,
Nicolas Chomont
Affiliations
Caroline Dufour
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada; Centre de Recherche du CHUM, Montreal, QC Canada
Maria Julia Ruiz
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada; Centre de Recherche du CHUM, Montreal, QC Canada
Amélie Pagliuzza
Centre de Recherche du CHUM, Montreal, QC Canada
Corentin Richard
Centre de Recherche du CHUM, Montreal, QC Canada
Aniqa Shahid
Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada; British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada
Rémi Fromentin
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada; Centre de Recherche du CHUM, Montreal, QC Canada
Rosalie Ponte
Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC, Canada; Research Institute of McGill University Health Centre, Montreal, QC, Canada
Amélie Cattin
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada; Centre de Recherche du CHUM, Montreal, QC Canada
Tomas Raul Wiche Salinas
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada; Centre de Recherche du CHUM, Montreal, QC Canada
Syim Salahuddin
Département de Sciences Biologiques, Université du Québec à Montréal, Montreal, QC, Canada
Teslin Sandstrom
Ottawa Hospital Research Institute, Ottawa, ON, Canada; Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, ON, Canada
Stephanie Burke Schinkel
Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, ON, Canada
Cecilia T. Costiniuk
Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC, Canada; Research Institute of McGill University Health Centre, Montreal, QC, Canada
Mohammad-Ali Jenabian
Département de Sciences Biologiques, Université du Québec à Montréal, Montreal, QC, Canada
Petronela Ancuta
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada; Centre de Recherche du CHUM, Montreal, QC Canada
Jean-Pierre Routy
Research Institute of McGill University Health Centre, Montreal, QC, Canada; Division of Hematology, McGill University Health Centre, Montreal, QC, Canada
Éric A. Cohen
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada; Institut de Recherches Cliniques de Montréal, Montreal, QC, Canada
Zabrina L. Brumme
Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada; British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada
Christopher Power
Department of Medicine (Neurology), University of Alberta, 6-11 Heritage Medical Research Center, Edmonton, AB, Canada; Department of Psychiatry, University of Alberta, Edmonton, AB, Canada
Jonathan B. Angel
Ottawa Hospital Research Institute, Ottawa, ON, Canada; Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, ON, Canada; Division of Infectious Diseases, Ottawa Hospital-General Campus, Ottawa, ON, Canada
Nicolas Chomont
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada; Centre de Recherche du CHUM, Montreal, QC Canada; Corresponding author
Summary: HIV persists in tissues during antiretroviral therapy (ART), but the relative contribution of different anatomical compartments to the viral reservoir in humans remains unknown. We performed an extensive characterization of HIV reservoirs in two men who donated their bodies to HIV cure research and who had been on suppressive ART for years. HIV DNA is detected in all tissues, with large variations across anatomical compartments and between participants. Intact HIV genomes represent 2% and 25% of all proviruses in the two participants and are mainly detected in secondary lymphoid organs, with the spleen and mediastinal lymph nodes harboring intact viral genomes in both individuals. Multiple copies of identical HIV genomes are found in all tissues, indicating that clonal expansions are common in anatomical sites. The majority (>85%) of these expanded clones are shared across multiple tissues. These findings suggest that infected cells expand, migrate, and possibly circulate between anatomical sites.
