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CD8+ lymphocytes do not impact SIV reservoir establishment under ART.
Statzu, Maura; Jin, Wang; Fray, Emily J; Wong, Andrew Kam Ho; Kumar, Mithra R; Ferrer, Elizabeth; Docken, Steffen S; Pinkevych, Mykola; McBrien, Julia B; Fennessey, Christine M; Keele, Brandon F; Liang, Shan; Harper, Justin L; Mutascio, Simona; Franchitti, Lavinia; Wang, Hong; Cicetti, Davide; Bosinger, Steven E; Carnathan, Diane G; Vanderford, Thomas H; Margolis, David M; Garcia-Martinez, J Victor; Chahroudi, Ann; Paiardini, Mirko; Siliciano, Janet; Davenport, Miles P; Kulpa, Deanna A; Siliciano, Robert S; Silvestri, Guido.
Affiliation
  • Statzu M; Emory National Primate Research Center, Department of Pathology and Laboratory Medicine, and Emory Vaccine Center, Emory University, Atlanta, GA, USA.
  • Jin W; Kirby Institute, University of New South Wales, Sydney, Australia.
  • Fray EJ; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Wong AKH; Emory National Primate Research Center, Department of Pathology and Laboratory Medicine, and Emory Vaccine Center, Emory University, Atlanta, GA, USA.
  • Kumar MR; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Ferrer E; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Docken SS; Kirby Institute, University of New South Wales, Sydney, Australia.
  • Pinkevych M; Kirby Institute, University of New South Wales, Sydney, Australia.
  • McBrien JB; Emory National Primate Research Center, Department of Pathology and Laboratory Medicine, and Emory Vaccine Center, Emory University, Atlanta, GA, USA.
  • Fennessey CM; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
  • Keele BF; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
  • Liang S; Emory National Primate Research Center, Department of Pathology and Laboratory Medicine, and Emory Vaccine Center, Emory University, Atlanta, GA, USA.
  • Harper JL; Emory National Primate Research Center, Department of Pathology and Laboratory Medicine, and Emory Vaccine Center, Emory University, Atlanta, GA, USA.
  • Mutascio S; Emory National Primate Research Center, Department of Pathology and Laboratory Medicine, and Emory Vaccine Center, Emory University, Atlanta, GA, USA.
  • Franchitti L; Emory National Primate Research Center, Department of Pathology and Laboratory Medicine, and Emory Vaccine Center, Emory University, Atlanta, GA, USA.
  • Wang H; Emory National Primate Research Center, Department of Pathology and Laboratory Medicine, and Emory Vaccine Center, Emory University, Atlanta, GA, USA.
  • Cicetti D; Emory National Primate Research Center, Department of Pathology and Laboratory Medicine, and Emory Vaccine Center, Emory University, Atlanta, GA, USA.
  • Bosinger SE; Emory National Primate Research Center, Department of Pathology and Laboratory Medicine, and Emory Vaccine Center, Emory University, Atlanta, GA, USA.
  • Carnathan DG; Emory National Primate Research Center, Department of Pathology and Laboratory Medicine, and Emory Vaccine Center, Emory University, Atlanta, GA, USA.
  • Vanderford TH; Emory National Primate Research Center, Department of Pathology and Laboratory Medicine, and Emory Vaccine Center, Emory University, Atlanta, GA, USA.
  • Margolis DM; Division of Infectious Diseases, Center for AIDS Research, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC, USA.
  • Garcia-Martinez JV; Division of Infectious Diseases, Center for AIDS Research, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC, USA.
  • Chahroudi A; Emory National Primate Research Center, Department of Pathology and Laboratory Medicine, and Emory Vaccine Center, Emory University, Atlanta, GA, USA.
  • Paiardini M; Department of Pediatrics, Emory University, Atlanta, GA, USA.
  • Siliciano J; Emory National Primate Research Center, Department of Pathology and Laboratory Medicine, and Emory Vaccine Center, Emory University, Atlanta, GA, USA.
  • Davenport MP; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Kulpa DA; Kirby Institute, University of New South Wales, Sydney, Australia.
  • Siliciano RS; Emory National Primate Research Center, Department of Pathology and Laboratory Medicine, and Emory Vaccine Center, Emory University, Atlanta, GA, USA.
  • Silvestri G; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nat Microbiol ; 8(2): 299-308, 2023 02.
Article in En | MEDLINE | ID: mdl-36690860
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.
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Full text: 1 Database: MEDLINE Main subject: HIV Infections / Simian Acquired Immunodeficiency Syndrome / Simian Immunodeficiency Virus Limits: Animals / Humans Language: En Journal: Nat Microbiol Year: 2023 Type: Article Affiliation country: United States
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Full text: 1 Database: MEDLINE Main subject: HIV Infections / Simian Acquired Immunodeficiency Syndrome / Simian Immunodeficiency Virus Limits: Animals / Humans Language: En Journal: Nat Microbiol Year: 2023 Type: Article Affiliation country: United States