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Persistent Viral Reservoirs in Lymphoid Tissues in SIV-Infected Rhesus Macaques of Chinese-Origin on Suppressive Antiretroviral Therapy

Journal Article · · Viruses
DOI:https://doi.org/10.3390/v11020105· OSTI ID:1628585
 [1];  [2];  [3];  [4];  [5];  [6];  [7]
  1. Tulane Primate Research Center, Covington, LA (United States). Division of Comparative Pathology; DOE/OSTI
  2. Tulane Primate Research Center, Covington, LA (United States). Division of Comparative Pathology
  3. Univ. of Western Ontario, London, ON (Canada). Department of Microbiology & Immunology, Schulich School of Medicine & Dentistry
  4. Tulane Primate Research Center, Covington, LA (United States). Division of Veterinary Medicine; Tulane Univ., New Orleans, LA (United States). Dept. of Medicine, School of Medicine
  5. Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Biology and Biophysics Group
  6. Univ. of Nebraska, Lincoln, NE (United States). Nebraska Center for Virology, School of Biological Sciences
  7. Tulane Primate Research Center, Covington, LA (United States). Division of Comparative Pathology; Tulane Univ., New Orleans, LA (United States). Tulane Center for Aging, School of Medicine; Tulane Univ., New Orleans, LA (United States). Department of Microbiology & Immunology, School of Medicine
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Understanding HIV latent reservoirs in tissues is essential for the development of new strategies targeting these sites for eradication. Here, we assessed the size of latent reservoirs and the source of residual viruses in multiple lymphoid tissues of SIV-infected and fully suppressed rhesus macaques of Chinese-origin (cRMs). Eight cRMs were infected with SIVmac251 and treated with tenofovir and emtricitabine daily for 24 weeks initiated 4 weeks post-infection. Four of the eight animals reached sustained full viral suppression with undetectable viremia. The levels of cell-associated SIV DNA varied in peripheral blood mononuclear cells (PBMCs) and multiple lymphoid tissues, but with higher levels in the mesenteric lymph nodes (MesLNs). The levels of cell-associated SIV RNA also varied in different tissues. The higher frequency of viral RNA detection in the MesLNs was also observed by in situ hybridization. Consistently, the infection unit per million cells (IUPM) in the MesLNs was higher than in PBMCs and other tested lymphoid tissues by quantitative viral outgrowth assay (QVOA). Furthermore, env gp120 from tissue SIV RNA was amplified by single genome amplification. Phylogenetic analysis revealed diverse variants from tissues parallel to the viral inoculum in all viral suppressed animals. These results demonstrate that the latency and viral reservoirs in the lymphoid tissues still exist in aviremic macaques under full suppressive therapy. Moreover, the size of viral latent reservoirs differs in various lymphoid tissues with a relatively larger size in the MesLNs.
Research Organization:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
National Institutes of Health; USDOE
Grant/Contract Number:
AC52-06NA25396
OSTI ID:
1628585
Journal Information:
Viruses, Journal Name: Viruses Journal Issue: 2 Vol. 11; ISSN 1999-4915; ISSN VIRUBR
Publisher:
MDPICopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (4)

Quantification of Viral RNA and DNA Positive Cells in Tissues From Simian Immunodeficiency Virus/Simian Human Immunodeficiency Virus Infected Controller and Progressor Rhesus Macaques journal December 2019
Current Status of Latency Reversing Agents Facing the Heterogeneity of HIV-1 Cellular and Tissue Reservoirs journal January 2020
Infectious Virus Persists in CD4 + T Cells and Macrophages in Antiretroviral Therapy-Suppressed Simian Immunodeficiency Virus-Infected Macaques journal May 2019
Evaluating the Intactness of Persistent Viral Genomes in Simian Immunodeficiency Virus-Infected Rhesus Macaques after Initiating Antiretroviral Therapy within One Year of Infection journal October 2019

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Related Subjects

60 APPLIED LIFE SCIENCES
Virology
antiretroviral therapy
lymph nodes
reservoir
rhesus macaques
simian immunodeficiency virus