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Cadena, Anthony M; Ventura, John D; Abbink, Peter; Borducchi, Erica N; Tuyishime, Hubert; Mercado, Noe B; Walker-Sperling, Victoria; Siamatu, Mazuba; Liu, Po-Ting; Chandrashekar, Abishek; Nkolola, Joseph P; McMahan, Katherine; Kordana, Nicole; Hamza, Venous; Bondzie, Esther A; Fray, Emily; Kumar, Mithra; Fischinger, Stephanie; Shin, Sally A; Lewis, Mark G; Siliciano, Robert F; Alter, Galit; Barouch, Dan H
Nature communications, 03/2021, Volume: 12, Issue: 1Journal Article
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.
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