Journal
MUCOSAL IMMUNOLOGY
Volume 13, Issue 1, Pages 149-160Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41385-019-0221-x
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Funding
- Canadian Institutes of Health Research (CIHR) [HBF-123682, HBF-126786, MOP-133476]
- ANRS (France)
- Canadian HIV Cure Enterprise Grant from the CIHR [HIG-133050]
- CANFAR
- IAS
- Laval University (Pierre-Jacob-Durand Grant)
- Laval University (Fonds de recherche sur le Sida)
- CHU de Quebec (Formation Desjardins pour la Recherche et l'Innovation)
- Fonds de Recherche du Quebec-Sante (FRQS)
- Fondation du CHU de Quebec
- Canada Research Chair program
- NIH [R21AI116200]
- National Institute of Allergy and Infectious Diseases of the National Institutes of Health [P51 OD011132]
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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-naive 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 SW 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.
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