Biology subjects

Pinyakorn, S.

Publications and source records attributed to Pinyakorn, S..

3 recordsLinked to original sources

bioRxiv2026

Unique CD8+ T Cell Populations Expand during ART and Predict Delayed HIV-1 Rebound

Antiretroviral therapy (ART) suppresses HIV-1 replication but does not eliminate the latent reservoir, resulting in viral rebound with variable kinetics after treatment interruption. How the immune cell states established during ART influences timing of rebound is not fully understood. In this study, we analyzed 111 participants across multiple cohorts, with 188 single-cell multiomic samples generated and integrated for joint analysis. Longitudinal profiling of peripheral blood mononuclear cells from individuals with acute HIV-1 infection on ART, spanning early infection through sustained therapy and pre-analytical treatment interruption, revealed that time to viral rebound was driven not by global changes in immune composition but by dynamic transcriptional programs within CD8+ T cells. During ART, there was a dramatic expansion of a unique cluster of poised naive CD8+ T cells, with a distinct immune state positioned upstream of stem-like memory CD8+ T cells along a cell differentiation continuum. The differential abundance of this poised naive CD8+ T cell population was enriched in participants with delayed rebound and showed strong predictive power for discriminating time to rebound. Mechanistically, the poised naive CD8+ T cells exhibited features of a precursor phenotype of stem-like memory CD8+ T cells, and showed activation of the TNF-NF-{kappa}B signaling pathway and increased chromatin accessibility at AP-1 motifs. Notably, both poised naive CD8+ T cells and stem-like memory CD8+ T cells were consistently enhanced during ART in both acute and chronic infection. In participants who received investigational therapeutic vaccination, the dominant predictive signal shifted downstream along the differentiation trajectory, with stem-like memory CD8+ T cells emerging as the primary determinant of delayed rebound. Together, these findings identify a dynamic CD8+ T cell state continuum as a central determinant of HIV-1 rebound, even in the absence of antigen-specificity, where ART establishes a predictive poised naive state that can be further leveraged by vaccination to enhance protective stem-like memory responses.

immunology↗

bioRxiv2022

Productive and latent HIV infections originate in resting CD4+ T cells

Productively and latently HIV-infected cells are the source of virus that respectively establishes and sustains systemic infections and the reservoir in which HIV persists and rebounds when anti-retroviral therapy (ART) is interrupted. While infected activated CD4+ T cells are thought to be the principal source of HIV production, and reversion of activated infected cells to a resting state as the major pathway to establishment of the latently infected cell reservoir, we now show that in the earliest stages of detectable HIV infection in the lymphoid tissue reservoir, infection of resting CD4+ T cells establishes the first populations of both productively and latently infected cells. We further show that the early infection of resting T cells reflects their predominance in lymphoid tissues and the expression of pTEFb in vivo in resting T cells to support their infection. The immediate establishment of productively and latently infected cell populations enable HIV to propagate and persist, and generates reservoirs from which infection can rebound despite instituting ART at the earliest stage of detectable infection.

immunology↗

bioRxiv2022

HIV rapidly targets a diverse pool of CD4+ T cells to establish productive and latent infections

Upon infection, HIV disseminates throughout the human body within 1-2 weeks. However, its early cellular targets remain poorly characterized. We analyzed productively and latently infected cells in blood and lymphoid tissue from individuals in acute infection. The phenotype of productively infected cells rapidly evolved with time and differed between blood and lymph nodes. The TCR repertoire of productively infected cells was heavily biased, with preferential infection of previously expanded/disseminated cells, but composed almost exclusively of unique clonotypes, indicating that they were the product of independent infection events. Latent genetically intact proviruses were already archived early in infection. Hence, productive infection is initially established in a pool of phenotypically and clonotypically distinct T cells in blood and lymph nodes and latently infected cells are generated simultaneously. One-Sentence SummaryHIV initially infects phenotypically and clonotypically distinct T cells and establishes a latent reservoir concomitantly.

microbiology↗