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

Nat Commun. 2021 Mar 5;12(1):1474. doi: 10.1038/s41467-021-21724-0.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Retroviral Agents / therapeutic use*
  • CD8-Positive T-Lymphocytes
  • DNA, Viral
  • Disease Models, Animal
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / virology*
  • HIV-1 / genetics
  • Lymph Nodes / immunology
  • Lymph Nodes / virology*
  • Lymphoid Tissue / virology
  • Macaca mulatta
  • Phylogeny
  • RNA, Viral / genetics*
  • Simian Acquired Immunodeficiency Syndrome / drug therapy
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Acquired Immunodeficiency Syndrome / virology*
  • Simian Immunodeficiency Virus / drug effects
  • Simian Immunodeficiency Virus / genetics
  • Simian Immunodeficiency Virus / immunology*
  • Viral Load
  • Virus Replication


  • Anti-Retroviral Agents
  • DNA, Viral
  • RNA, Viral