Myeloid and CD4 T Cells Comprise the Latent Reservoir in Antiretroviral Therapy-Suppressed SIVmac251-Infected Macaques

Author:

Abreu Celina M.1ORCID,Veenhuis Rebecca T.1,Avalos Claudia R.1,Graham Shelby1,Parrilla Daymond R.1,Ferreira Edna A.1,Queen Suzanne E.1,Shirk Erin N.1,Bullock Brandon T.1,Li Ming1,Metcalf Pate Kelly A.1ORCID,Beck Sarah E.1,Mangus Lisa M.1,Mankowski Joseph L.123,Mac Gabhann Feilim45,O’Connor Shelby L.6,Gama Lucio17,Clements Janice E.123

Affiliation:

1. Department of Molecular and Comparative Pathobiology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA

2. Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA

3. Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA

4. Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA

5. Institute for Computational Medicine, Johns Hopkins University, Baltimore, Maryland, USA

6. Department of Pathology and Laboratory Medicine, University of Wisconsin—Madison, Madison, Wisconsin, USA

7. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA

Abstract

This study provides further evidence that the latent reservoir is comprised of both CD4 + T cells and myeloid cells. The data presented here suggest that CD4 + T cells and macrophages found throughout tissues in the body can contain replication-competent SIV and contribute to rebound of the virus after treatment interruption. Additionally, we have shown that monocytes in blood contain latent virus and, though not considered a reservoir themselves due to their short life span, could contribute to the size of the latent reservoir upon entering the tissue and differentiating into long-lived macrophages. These new insights into the size and location of the SIV reservoir using a model that is heavily studied in the HIV field could have great implications for HIV-infected individuals and should be taken into consideration with the development of future HIV cure strategies.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | NIH | National Institute of Neurological Disorders and Stroke

HHS | NIH | National Institute of Mental Health

NSF | Office of the Director

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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