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. LewisRobert F. Siliciano, Galit Alter, Dan H. Barouch

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number1474
JournalNature communications
Volume12
Issue number1
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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