1. Persistence of viral RNA in lymph nodes in ART-suppressed SIV/SHIV-infected Rhesus Macaques
- Author
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Anthony M. Cadena, Po-Ting Liu, Robert F. Siliciano, Galit Alter, Emily J. Fray, John D. Ventura, Nicole Kordana, Katherine McMahan, Hubert Tuyishime, Peter Abbink, Sally Shin, Victoria Walker-Sperling, Joseph P. Nkolola, Noe B. Mercado, Dan H. Barouch, Mazuba Siamatu, Mithra Kumar, Erica N. Borducchi, Venous Hamza, Abishek Chandrashekar, Mark G. Lewis, Esther A. Bondzie, and Stephanie Fischinger
- Subjects
0301 basic medicine ,Lymphoid Tissue ,Science ,T cell ,viruses ,Simian Acquired Immunodeficiency Syndrome ,General Physics and Astronomy ,HIV Infections ,Biology ,CD8-Positive T-Lymphocytes ,Virus Replication ,General Biochemistry, Genetics and Molecular Biology ,Article ,Persistence (computer science) ,03 medical and health sciences ,Viral reservoirs ,0302 clinical medicine ,Transcription (biology) ,medicine ,Animals ,Phylogeny ,Multidisciplinary ,CD69 ,virus diseases ,General Chemistry ,Viral Load ,Virology ,Macaca mulatta ,Cellular immunity ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Viral replication ,Anti-Retroviral Agents ,Viral evolution ,DNA, Viral ,HIV-1 ,RNA, Viral ,Female ,Simian Immunodeficiency Virus ,Lymph ,Lymph Nodes ,030217 neurology & neurosurgery ,CD8 - Abstract
The establishment of a long-lived viral reservoir is the key obstacle for achieving an HIV-1 cure. However, the anatomic, virologic, and immunologic features of the viral reservoir in tissues during antiretroviral therapy (ART) remain poorly understood. Here we present a comprehensive necroscopic analysis of the SIV/SHIV viral reservoir in multiple lymphoid and non-lymphoid tissues from SIV/SHIV-infected rhesus macaques suppressed with ART for one year. Viral DNA is observed broadly in multiple tissues and is comparable in animals that had initiated ART at week 1 or week 52 of infection. In contrast, viral RNA is restricted primarily to lymph nodes. Ongoing viral RNA transcription is not the result of unsuppressed viral replication, as single-genome amplification and subsequent phylogenetic analysis do not show evidence of viral evolution. Gag-specific CD8+ T cell responses are predominantly observed in secondary lymphoid organs in animals chronically infected prior to ART and these responses are dominated by CD69+ populations. Overall, we observe that the viral reservoir in rhesus macaques is widely distributed across multiple tissue sites and that lymphoid tissues act as a site of persistent viral RNA transcription under conditions of long-term ART suppression., The existence of HIV reservoir and ongoing replication despite antiretroviral therapy (ART) represents a barrier for cure efforts. Here, using SIV/SHIV-infected rhesus macaque suppressed with ART for one year, the authors characterize multiple lymphoid and non-lymphoid tissues and show that while the viral reservoir exhibits a wide anatomic heterogeneity, persistent viral transcription is mainly restricted to secondary lymphoid organs.
- Published
- 2021