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

Siddiqui, Summer; Perez, Stefanie; Gao, Yong; Doyle-Meyers, Lara; Foley, Brian; Li, Qingsheng; Ling, Binhua

doi:10.3390/v11020105

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

Journal Article · 27 January 2019 · Viruses

DOI: https://doi.org/10.3390/v11020105 · OSTI ID:1628585

Siddiqui, Summer ^[1]; Perez, Stefanie ^[2]; Gao, Yong ^[3]; Doyle-Meyers, Lara ^[4]; Foley, Brian ^[5];

^[6]; Ling, Binhua ^[7]

Tulane Primate Research Center, Covington, LA (United States). Division of Comparative Pathology; DOE/OSTI
Tulane Primate Research Center, Covington, LA (United States). Division of Comparative Pathology
Univ. of Western Ontario, London, ON (Canada). Department of Microbiology & Immunology, Schulich School of Medicine & Dentistry
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
Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Biology and Biophysics Group
Univ. of Nebraska, Lincoln, NE (United States). Nebraska Center for Virology, School of Biological Sciences
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

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.

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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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HIV-infected individuals receiving effective antiviral therapy for extended periods of time continually replenish their viral reservoir Chun, T. -W. Journal of Clinical Investigation, Vol. 115, Issue 11 https://doi.org/10.1172/jci26197	journal	November 2005
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Humanized mice: models for evaluating NeuroHIV and cure strategies Honeycutt, Jenna B.; Garcia, J. Victor Journal of NeuroVirology, Vol. 24, Issue 2 https://doi.org/10.1007/s13365-017-0567-3	journal	August 2017
Persistence of SIV in the brain of SIV-infected Chinese rhesus macaques with or without antiretroviral therapy Perez, Stefanie; Johnson, Ann-Marie; Xiang, Shi-hua Journal of NeuroVirology, Vol. 24, Issue 1 https://doi.org/10.1007/s13365-017-0594-0	journal	November 2017
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Lymph nodes harbor viral reservoirs that cause rebound of plasma viremia in SIV-infected macaques upon cessation of combined antiretroviral therapy Horiike, Mariko; Iwami, Shingo; Kodama, Makoto Virology, Vol. 423, Issue 2 https://doi.org/10.1016/j.virol.2011.11.024	journal	February 2012
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Effect of Antiretroviral Therapy on HIV Reservoirs in Elite Controllers Chun, Tae-Wook; Shawn Justement, J.; Murray, Danielle The Journal of Infectious Diseases, Vol. 208, Issue 9 https://doi.org/10.1093/infdis/jit306	journal	July 2013
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HIV-infected individuals receiving effective antiviral therapy for extended periods of time continually replenish their viral reservoir Chun, T. -W. Journal of Clinical Investigation, Vol. 115, Issue 11 https://doi.org/10.1172/JCI26197	journal	November 2005
A mature macrophage is a principal HIV-1 cellular reservoir in humanized mice after treatment with long acting antiretroviral therapy Araínga, Mariluz; Edagwa, Benson; Mosley, R. Lee Retrovirology, Vol. 14, Issue 1 https://doi.org/10.1186/s12977-017-0344-7	journal	March 2017
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Analysis of Multiply Spliced Transcripts in Lymphoid Tissue Reservoirs of Rhesus Macaques Infected with RT-SHIV during HAART Deere, Jesse D.; Kauffman, Robert C.; Cannavo, Elda PLoS ONE, Vol. 9, Issue 2 https://doi.org/10.1371/journal.pone.0087914	journal	February 2014
Effects of Treatment with Suppressive Combination Antiretroviral Drug Therapy and the Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid; (SAHA) on SIV-Infected Chinese Rhesus Macaques Ling, Binhua; Piatak, Michael; Rogers, Linda PLoS ONE, Vol. 9, Issue 7 https://doi.org/10.1371/journal.pone.0102795	journal	July 2014
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Title: Persistent Viral Reservoirs in Lymphoid Tissues in SIV-Infected Rhesus Macaques of Chinese-Origin on Suppressive Antiretroviral Therapy

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