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1277 Results
Background Despite the efficient suppression of HIV-1 replication with combined antiretroviral therapy, viral latency is a barrier to HIV cure. Bispecific antibodies against Env and CD3 have resulted in the ex vivo killing of HIV-containing cells from PLWH. However, the low level of Env expression on the cell surface and the sequence variation in the…
Background Natural killer (NK) cells respond rapidly in early HIV-1 infection. HIV-1 suppression and functional cure strategies can be developed by exploiting the intrinsic function of NK cells in recognizing HIV-infected cells. In our previous work, we profiled the phenotype of human primary NK cells responsive to autologous HIV-1-infected CD4+ T cells in vitro. We…
Background Latency-reversing agents (LRAs) have shown promise in reactivating HIV reservoir within “shock and kill”approaches. However, molecular mechanisms underlying HIV reactivation within CD4+ T cells as well as predictors of LRA efficacy remain partially unknown. Here, we investigated the transcriptomic and whole genome DNA methylation profile of CD4+ T cells cultured in vitro with or…
Background HIV-1 persists despite effective ART due to a reservoir of latently infected CD4+ T cells. Previous studies suggest that intact proviruses integrated in heterochromatic regions are progressively enriched during long-term ART. These proviruses may evade immune recognition due to lower viral gene expression, but their clinical significance upon ART interruption is unclear. Given the…
Background In recent years there have been significant advances in the development of assays to quantify and characterize the HIV-1 reservoir. As these assays are incorporated into HIV-1 cure clinical trials, ensuring the reliability and reproducibility of assay results across different laboratories becomes crucial. This study aimed to evaluate the inter-laboratory performance of assays measuring…
Background Accumulating evidence supports that the establishment and persistence of HIV latent reservoirs despite suppressive ART are intricately linked to the quiescent metabolism of CD4+ memory T cells. We investigated whether reprogramming T cell metabolism towards aerobic glycolysis could facilitate HIV latency reversal from circulating viral reservoirs. We used Zaprinast, a Mitochondrial Pyruvate Carrier inhibitor,…
Background HIV-1 persistence poses a significant barrier to HIV eradication. Findings from the largest post-mortem study (FIND 2.0), which utilized minimally invasive tissue sampling in 38 virally suppressed individuals on antiretroviral therapy (ART) (VS; <400 copies/mL) and 22 unsuppressed (VU) untreated individuals showed the presence of proviral DNA in all 11 anatomically distinct compartments. We report detailed genotypic…
Background HIV-1 cure strategies require a comprehensive understanding of cellular phenotype of HIV tissue reservoirs for effective and selective targeting. While recent data have demonstrated the highly heterogeneous nature of peripheral blood CD4+ T cells subsets comprising the HIV reservoir of antiretroviral therapy (ART) treated people with HIV (PWH), CD4+ T follicular helper (Tfh) cells…
Background There is a paucity of understanding of how HIV latent reservoirs survive and expand, escape immune clearance, and reactivate upon ART cessation. The integration site (IS) of proviral DNA into the host genome could (i) determine the transcriptional status of the provirus and (ii) influence the expansion of infected cells. In this study, we…
Background Characterization of HIV-1 persistence in both CD4+ T cell and myeloid reservoirs within systemic tissues and the brain are goals of the cure field. Clade D HIV-1 infects both CD4+ T cells and macrophages. Thus, we have employed SHIV encoding a clade D transmitted/founder HIV-1 Env to study reservoirs in ART-suppressed rhesus macaques (RM).…