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Author Notes:

Corresponding Author: Dr. Guido Silvestri, Yerkes National Primate Research Center, Emory University School of Medicine, 929 Gatewood Rd, Atlanta, GA 30329, gsilves@emory.edu, Phone: 404-727-7217 fax: 404-727-7768

E.K.C. and G.S. designed and performed the experiments.

L.S., S.A.S., S.P., and C.D. performed single genome sequencing of SIV-RNA.

D.L., S.E.B., and T.H.V. performed deep sequencing of cell-associated SIV-DNA. R.F. and J.D.L performed ultrasensitive viral load analyses.

B.O.L, M.N, and T.H.V. performed viral load and cell-associated DNA analyses.

K.E performed statistical analyses.

J.D.E. performed RNAscope analysis.

J.E.S., M.P., A.C., C.D., and S.E.B. discussed the data.

E.K.C., A.C., and G.S. wrote the manuscript.

We thank J. Levy, D.G. Carnathan, M. Mavigner, C.S. McGary and G. Mylvaganam for helpful discussions; B. Cervasi, K. P. Gill and J.P. Mackel for technical support; S. Ehnert for study organization and scheduling; YNPRC veterinary staff, especially S. Jean for caring for the animals and daily ART administration; Merck (I.MTA.14.232) Gilead Sciences (I.MTA.14.230), and Janssen R&D Ireland (I.MTA.14.231) for generously providing Raltegravir, PMPA and FTC, and Darunavir, respectively.

We thank the Emory CFAR Virology core for viral loads and the Emory CFAR Immunology core for use of the MiSeq platform.

The authors declare no conflicts of interest.

Subjects:

Research Funding:

This work was funded in part by R01-AI90797 (to G.S.), RR000165/OD011132 to the YNPRC, the Emory CFAR, NIH Grant # P30-AI-504, R01 AI-58706 and U19 AI-109633 (to C.D.) and supported in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E (J.L.).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • SIMIAN IMMUNODEFICIENCY VIRUS
  • T-CELL DEPLETION
  • MHC CLASS-I
  • RHESUS MACAQUES
  • CYCLOSPORINE-A
  • HIV-INFECTION
  • MONOCLONAL-ANTIBODY
  • PLASMA VIREMIA
  • IMMUNE CONTROL
  • REPLICATION

CD8(+) Lymphocytes Are Required for Maintaining Viral Suppression in SIV-Infected Macaques Treated with Short-Term Antiretroviral Therapy

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Journal Title:

Immunity

Volume:

Volume 45, Number 3

Publisher:

, Pages 656-668

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Infection with HIV persists despite suppressive antiretroviral therapy (ART), and treatment interruption results in rapid viral rebound. Antibody-mediated CD8 + lymphocyte depletion in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) shows that these cells contribute to viral control in untreated animals. However, the contribution of CD8 + lymphocytes to maintaining viral suppression under ART remains unknown. Here, we have shown that in SIV-in fected RMs treated with short-term (i.e., 8–32 week) ART, depletion of CD8 + lymphocytes resulted in increased plasma viremia in all animals and that repopulation of CD8 + T cells was associated with prompt reestablishment of virus control. Although the number of SIV-DNA-positive cells remained unchanged after CD8 depletion and reconstitution, the frequency of SIV-infected CD4 + T cells before depletion positively correlated with both the peak and area under the curve of viremia after depletion. These results suggest a role for CD8 + T cells in controlling viral production during ART, thus providing a rationale for exploring immunotherapeutic approaches in ART-treated HIV-infected individuals.

Copyright information:

© 2016 Elsevier Inc.

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