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

Henintsoa Rabezanahary,Guido Silvestri,Gina Racine,David Palesch,Ouafa Zghidi-Abouzid,Calayselvy Soundaramourty,Jérôme Estaquier,Julien Clain,Félicien Moukambi,Guadalupe Andreani,Cécile Tremblay,Ghita Benmadid-Laktout

doi:10.1038/s41385-019-0221-x

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.

Highlights

To date, the identification of cellular and anatomic reservoirs and their eradication remains a major challenge for an HIV cure.[1]
Frequencies of cell-associated viral DNA in lymphoid organs of acutely infected rhesus macaques (RMs) Twelve (12) RMs were infected with 20 AID50 of SIVmac[251] and sacrificed at day 4, 7, 11, 14, 18, and 30 post infection, with 2 monkeys examined at each time point to determine the early simian immunodeficiency virus (SIV) seeding in lymphoid tissues (Table 1)
Viral DNA was detected at day 7, mainly in that effector memory (TEM), TFH, and TCM populations isolated from the spleen of SIV-infected RMs (Fig. 1a); viral DNA was not detected in mesenteric and peripheral lymph nodes (LNs) at day 7

Summary

Introduction

The identification of cellular and anatomic reservoirs and their eradication remains a major challenge for an HIV cure.[1]. Mesenteric LNs are essential for oral tolerance.[35,36] very little focus has been given to these regions in respect to elucidating their role for the VR

Methods

Results

Conclusion