biostudies-literatureCadena AMNIAID NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious DiseasesNIH HHS1474https://www.ebi.ac.uk/biostudies/studies/S-EPMC7935896biostudies-literatureUnknown12(1)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.Nature communicationsPersistence of viral RNA in lymph nodes in ART-suppressed SIV/SHIV-infected Rhesus Macaques.PMC7935896U19 AI128751R01 AI129797UM1 AI124377R01 OD024917P01 AI131306AI124377, AI126603, AI128751, AI129797, OD024917UM1 AI126603McMahan KFischinger SLiu PTBorducchi ENShin SACadena AMWalker-Sperling VBarouch DHKordana NKumar MLewis MGTuyishime HMercado NBHamza VFray EAlter GAbbink PVentura JDSiliciano RFSiamatu MBondzie EANkolola JPChandrashekar AfalsePersistence of viral RNA in lymph nodes in ART-suppressed SIV/SHIV-infected Rhesus Macaques.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.2021-01-01T00:00:00Z2021 Mar2025-04-21T18:06:32.532Z2025-04-05T17:05:05.846ZS-EPMC79358963367457210.1038/s41467-021-21724-0