Characterization of Intact Proviruses in Blood and Lymph Node from HIV-Infected Individuals Undergoing Analytical Treatment Interruption

Author:

Vibholm Line K.123ORCID,Lorenzi Julio C. C.3,Pai Joy A.3,Cohen Yehuda Z.3ORCID,Oliveira Thiago Y.3,Barton John P.4,Garcia Noceda Marco4,Lu Ching-Lan3,Ablanedo-Terrazas Yuria5,Del Rio Estrada Perla M.5,Reyes-Teran Gustavo5,Tolstrup Martin12,Denton Paul W.12,Damsgaard Tine1,Søgaard Ole S.12,Nussenzweig Michel C.36

Affiliation:

1. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

2. Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark

3. Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA

4. Department of Physics and Astronomy, University of California, Riverside, California, USA

5. Center for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, Mexico

6. Howard Hughes Medical Institute, The Rockefeller University, New York, New York, USA

Abstract

HIV-1 persists as a latent infection in CD4 + T cells that can be found in lymphoid tissues in infected individuals during ART. However, the importance of this tissue reservoir and its contribution to viral rebound upon ART interruption are not clear. In this study, we sought to compare latent HIV-1 from blood and lymph node CD4 + T cells from five HIV-1-infected individuals. Further, we analyzed the contribution of lymph node viruses to viral rebound. We observed that the frequencies of intact proviruses were the same in blood and lymph node. Moreover, expanded clones of T cells bearing identical proviruses were found in blood and lymph node. These latent reservoir sequences did not appear to be the direct origin of rebound virus. Instead, latent proviruses were found to contribute to the rebound compartment by recombination.

Funder

Danish Council for Independent Research

The Bill and Melinda Gates Foundation for AIDS Vaccine Discovery

National Institute of Health

Einstein-Rockefeller-CUNY Center for AIDS Research

BEAT-HIV Delaney Grant

Robertson Fund

HHS | NIH | National Institute of Allergy and Infectious Diseases

Aarhus Universitet

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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