Despite early antiretroviral therapy effector memory and follicular helper CD4 T cells are major reservoirs in visceral lymphoid tissues of SIV-infected macaques

Mucosal Immunol. 2020 Jan;13(1):149-160. doi: 10.1038/s41385-019-0221-x. Epub 2019 Nov 13.


Whereas antiretroviral therapy (ART) suppresses viral replication, ART discontinuation results in viral rebound, indicating the presence of viral reservoirs (VRs) established within lymphoid tissues. Herein, by sorting CD4 T-cell subsets from the spleen, mesenteric and peripheral lymph nodes (LNs) of SIVmac251-infected rhesus macaques (RMs), we demonstrate that effector memory (TEM) and follicular helper (TFH) CD4+ T cells harbor the highest frequency of viral DNA and RNA, as well of early R-U5 transcripts in ART-naïve RMs. Furthermore, our results highlight that these two CD4 T cells subsets harbor viral DNA and early R-U5 transcripts in the spleen and mesenteric LNs (but not in peripheral LN) of RMs treated with ART at day 4 post infection suggesting that these two anatomical sites are important for viral persistence. Finally, after ART interruption, we demonstrate the rapid and, compared to peripheral LNs, earlier seeding of SIV in spleen and mesenteric LNs, thereby emphasizing the importance of these two anatomical sites for viral replication dynamics. Altogether our results advance understanding of early viral seeding in which visceral lymphoid tissues are crucial in maintaining TEM and TFH VRs.

Publication types

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

MeSH terms

  • Animals
  • Anti-Retroviral Agents
  • CD4-Positive T-Lymphocytes / physiology*
  • CD4-Positive T-Lymphocytes / virology
  • DNA, Viral / genetics
  • Disease Reservoirs
  • Germinal Center / immunology*
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / physiology*
  • Humans
  • Immunologic Memory
  • Lymphoid Tissue / physiology*
  • Lymphoid Tissue / virology
  • Macaca
  • RNA, Small Nuclear / genetics
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / physiology*
  • Spleen / physiology*
  • Spleen / virology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Viral Load
  • Virus Replication
  • Viscera / immunology*


  • Anti-Retroviral Agents
  • DNA, Viral
  • RNA, Small Nuclear
  • U5 small nuclear RNA