Persistence of viral RNA in lymph nodes in ART-suppressed SIV/SHIV-infected Rhesus Macaques

Anthony M. Cadena, John D. Ventura, Peter Abbink, Erica N. Borducchi, Hubert Tuyishime, Noe B. Mercado, Victoria Walker-Sperling, Mazuba Siamatu, Po-Ting Liu, Abishek Chandrashekar, Joseph P. Nkolola, Katherine McMahan, Nicole Kordana, Venous Hamza, Esther A. Bondzie, Emily Fray, Mithra Kumar, Stephanie Fischinger, Sally A. Shin, Mark G. Lewis, Robert F. Siliciano, Galit Alter and Dan H. Barouch ()
Additional contact information
Anthony M. Cadena: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School
John D. Ventura: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School
Peter Abbink: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School
Erica N. Borducchi: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School
Hubert Tuyishime: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School
Noe B. Mercado: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School
Victoria Walker-Sperling: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School
Mazuba Siamatu: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School
Po-Ting Liu: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School
Abishek Chandrashekar: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School
Joseph P. Nkolola: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School
Katherine McMahan: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School
Nicole Kordana: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School
Venous Hamza: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School
Esther A. Bondzie: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School
Emily Fray: Johns Hopkins University School of Medicine
Mithra Kumar: Johns Hopkins University School of Medicine
Stephanie Fischinger: Ragon Institute of MGH, MIT, and Harvard
Sally A. Shin: Ragon Institute of MGH, MIT, and Harvard
Mark G. Lewis: Bioqual
Robert F. Siliciano: Johns Hopkins University School of Medicine
Galit Alter: Ragon Institute of MGH, MIT, and Harvard
Dan H. Barouch: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-21724-0

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