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

1
Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA 70433, USA
2
Department of Microbiology & Immunology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada
3
Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, LA 70433, USA
4
Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA
5
Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
6
Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA
7
Tulane Center for Aging, Tulane University School of Medicine, New Orleans, LA 70112, USA
8
Department of Microbiology & Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA
*
Author to whom correspondence should be addressed.
Current address: Hayward Genetics Center, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Viruses 2019, 11(2), 105; https://doi.org/10.3390/v11020105
Received: 20 December 2018 / Revised: 21 January 2019 / Accepted: 24 January 2019 / Published: 27 January 2019
(This article belongs to the Section Animal Viruses)
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. View Full-Text
Keywords: simian immunodeficiency virus; rhesus macaques; lymph nodes; reservoir; antiretroviral therapy simian immunodeficiency virus; rhesus macaques; lymph nodes; reservoir; antiretroviral therapy
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MDPI and ACS Style

Siddiqui, S.; Perez, S.; Gao, Y.; Doyle-Meyers, L.; Foley, B.T.; Li, Q.; Ling, B. Persistent Viral Reservoirs in Lymphoid Tissues in SIV-Infected Rhesus Macaques of Chinese-Origin on Suppressive Antiretroviral Therapy. Viruses 2019, 11, 105.

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