CD8(+) lymphocytes do not impact SIV reservoir establishment under ART

• Type of Material: Article
• Authors: Maura Statzu, Emory University; Wang Jin, University of New South Wales; Emily J Fray, Johns Hopkins University; Andrew Kam Ho Wong, Emory University; Mithra R Kumar, Johns Hopkins University; Elizabeth Ferrer, Johns Hopkins University; Steffen S Docken, University of New South Wales; Mykola Pinkevych, University of New South Wales; Julia B McBrien, Emory University; Christine M Fennessey, Frederick National Laboratory for Cancer Research; Brandon F Keele, Frederick National Laboratory for Cancer Research; Shan Liang, Emory University; Justin L Harper, Emory University; Simona Mutascio, Emory University; Lavinia Franchitti, Emory University; Hong Wang, Emory University; Davide Cicetti, Emory University; Steven Bosinger, Emory University; Diane G Carnathan, Emory University; Thomas Vanderford, Emory University; David M Margolis, University of North Carolina Chapel Hill; Victor J Garcia-Martinez, University of North Carolina Chapel Hill; Ann Chahroudi, Emory University; Mirko Paiardini, Emory University; Janet Siliciano, Johns Hopkins University; Miles P Davenport, Univ New South Wales; Deanna Kulpa, Emory University; Robert S Siliciano, Johns Hopkins University; Guido Silvestri, Emory University
• Language: English
• Date: 2023-01-23
• Publisher: NATURE PORTFOLIO
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2023
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41564-022-01311-9
• Title of Journal or Parent Work: NATURE MICROBIOLOGY
• Volume: 8
• Issue: 2
• Start Page: 299
• End Page: 308
• Keywords: DEPLETION; Science & Technology; ESCAPE; Microbiology; T-CELLS; Life Sciences & Biomedicine; VIREMIA; HIV-1; INFECTION; SUPPRESSION; REPLICATION; HUMAN-IMMUNODEFICIENCY-VIRUS; DYNAMICS
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Persistence of the human immunodeficiency virus type-1 (HIV-1) latent reservoir in infected individuals remains a problem despite fully suppressive antiretroviral therapy (ART). While reservoir formation begins during acute infection, the mechanisms responsible for its establishment remain unclear. CD8+ T cells are important during the initial control of viral replication. Here we examined the effect of CD8+ T cells on formation of the latent reservoir in simian immunodeficiency virus (SIV)-infected macaques by performing experimental CD8+ depletion either before infection or before early (that is, day 14 post-infection) ART initiation. We found that CD8+ depletion resulted in slower decline of viremia, indicating that CD8+ lymphocytes reduce the average lifespan of productively infected cells during acute infection and early ART, presumably through SIV-specific cytotoxic T lymphocyte (CTL) activity. However, CD8+ depletion did not change the frequency of infected CD4+ T cells in the blood or lymph node as measured by the total cell-associated viral DNA or intact provirus DNA assay. In addition, the size of the persistent reservoir remained the same when measuring the kinetics of virus rebound after ART interruption. These data indicate that during early SIV infection, the viral reservoir that persists under ART is established largely independent of CTL control.