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

• Type of Material: Article
• Authors: Henintsoa Rabezanahary, Laval University; Felicien Moukambi, Laval University; David Palesch, Emory University; Julien Clain, Laval University; Gina Racine, Laval University; Guadalupe Andreani, Laval University; Ghita Benmadid-Laktout, Laval University; Ouafa Zghidi-Abouzid, Laval University; Calaysalvy Soundaramourty, Université Paris Descartes; Cecile Tremblay, Université de Montréal; Guido Silvestri, Emory University; Jerome Estaquier, Laval University
• Language: English
• Date: 2020-01-01
• Publisher: NATURE PUBLISHING GROUP
• Publication Version: Final Published Version
• Copyright Statement: © 2019, The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41385-019-0221-x
• Title of Journal or Parent Work: MUCOSAL IMMUNOLOGY
• Volume: 13
• Issue: 1
• Start Page: 149
• End Page: 160
• Grant/Funding Information: J.C. was supported by a fellowship from Laval University (Pierre-Jacob-Durand Grant and Fonds de recherche sur le Sida).; J.E. also thanks the Canada Research Chair program for financial assistance.; F.M. was supported by a fellowship from the Fondation du CHU de Québec.; This work was supported by grants from the Canadian Institutes of Health Research (CIHR) (HBF-123682, HBF-126786, and MOP-133476), the ANRS (France), and by the Canadian HIV Cure Enterprise Grant HIG-133050 from the CIHR partnership with CANFAR and IAS to J.E.; H.R. was supported by a fellowship from Laval University (Pierre-Jacob-Durand Grant and Fonds de recherche sur le Sida), CHU de Québec (Formation Desjardins pour la Recherche et l’Innovation), and Fonds de Recherche du Québec—Santé (FRQS).; The work from Yerkes National Primate Research Center was funded by NIH grant R21AI116200, as well as, supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number P51 OD011132 (to the YNPRC) to G.S.
• Keywords: DYNAMICS; Science & Technology; IMMUNODEFICIENCY VIRUS-INFECTION; PERSISTENCE; PROVIRUSES; Life Sciences & Biomedicine; Immunology; LYMPHOCYTES; REPLICATION-COMPETENT HIV-1; PROLIFERATION; APOPTOSIS; LATENT RESERVOIR; NODES
• Research Categories: Biology, Virology; Health Sciences, Immunology

Abstract

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.