Clonal dynamics of HIV-infected and uninfected T cells

作者：S. L. Weissman, Ashley M. Ginda, Alfonso Oceguera, Liam Swiggard, Marilia Rita Pinzone, LaMont Cannon, Ryan Zurakowski, Stephen A. Migueles, Frederic D. Bushman, Una O'Doherty · 发表于：EBioMedicine · 年份：2026 · DOI：10.1016/j.ebiom.2026.106163 · 被引用次数：1 · 研究领域：HIV Research and Treatment、T-cell and B-cell Immunology、Immune Cell Function and Interaction

BACKGROUND: The HIV reservoir was once considered to be transcriptionally silent. Evidence is emerging that a substantial portion of the reservoir is transcriptionally active. We explore the consequences of transcriptionally active proviruses on the infected T cell by longitudinally monitoring the fate of proviral clones. METHODS: We analysed proviral dynamics by monitoring ∼4000 HIV proviral sequences and ∼13,000 integration site sequences along with ∼2 million T cell receptor (TCR) sequences in up to 9 people living with HIV over time. This analysis includes 7 chronically treated and 2 elite controller participants, with paired TCR sequencing in 6 individuals. We also analysed 9 participants from published cohorts. Our analysis used a Morisita metric to capture contraction and expansion of proviral clones. The role of HIV expression was also investigated by studying the effect of integration site and orientation indirectly in vivo and directly in a cell line model. FINDINGS: We focus on cell-intrinsic forces and provide evidence that proviral clones contract and expand more in individuals treated during chronic infection compared to elite controllers. Moreover, proviral clones change more than TCR clones suggesting a subset of infected cells may turnover more than uninfected cells. We also provide evidence of two opposing forces, both initiated by HIV expression within the cell, likely contributing to proviral dynamics. These forces could explain the increased changes in pr...