Abstract
Understanding HIV latent reservoirs in tissues is essential for the development of new strategies targeting these sites for eradication. Here, we assessed the size of latent reservoirs and the source of residual viruses in multiple lymphoid tissues of SIV-infected and fully suppressed rhesus macaques of Chinese-origin (cRMs). Eight cRMs were infected with SIVmac251 and treated with tenofovir and emtricitabine daily for 24 weeks initiated 4 weeks post-infection. Four of the eight animals reached sustained full viral suppression with undetectable viremia. The levels of cell-associated SIV DNA varied in peripheral blood mononuclear cells (PBMCs) and multiple lymphoid tissues, but with higher levels in the mesenteric lymph nodes (MesLNs). The levels of cell-associated SIV RNA also varied in different tissues. The higher frequency of viral RNA detection in the MesLNs was also observed by in situ hybridization. Consistently, the infection unit per million cells (IUPM) in the MesLNs was higher than in PBMCs and other tested lymphoid tissues by quantitative viral outgrowth assay (QVOA). Furthermore, env gp120 from tissue SIV RNA was amplified by single genome amplification. Phylogenetic analysis revealed diverse variants from tissues parallel to the viral inoculum in all viral suppressed animals. These results demonstrate that the latency and viral reservoirs in the lymphoid tissues still exist in aviremic macaques under full suppressive therapy. Moreover, the size of viral latent reservoirs differs in various lymphoid tissues with a relatively larger size in the MesLNs.
Highlights
The viral latent reservoir remains a key barrier in HIV-1 eradication [1]
Viremia peaked at 2 weeks post-infection to the median of 8.5 × 106 copies/mL with the highest plasma viral loads (pVL)
It has been demonstrated that lymph nodes have the most latently infected memory CD4+ T cells among tissue reservoirs in HIV-1-infected individuals and SIV-infected macaques on fully suppressive combination antiretroviral therapy (cART), we found that the viral reservoir distribution in different lymphoid tissues were at different levels in this SIV/cRM/antiretroviral therapy (ART) model, parallel to other SIVsusceptible NHP models, making it serve as an important model for HIV persistence and cure research
Summary
Combination antiretroviral therapy (cART) can effectively suppress the viral replication to undetectable levels in peripheral blood, the current antiretroviral drugs are unable to eliminate cellular and tissue latent reservoirs even with the earliest cART during hyperacute HIV infection [2]. Lymph nodes (LNs), the spleen, gut-associated lymphoid tissues, the reproductive system, and the central nervous system are proposed to account for viral persistence [5]. HIV persists in follicular dendritic cells by trapping viable virions on their surface and in follicular helper CD4+ T cells inside the germinal center of the LNs in HIV-infected patients with suppressive cART [7,8] or in the lymphoid tissues in aviremic patients on cART [9], indicating that the low-level ongoing virus replication may be another source of plasma virus rebound after cessation of ART
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
