Postdoctoral Associate The Jackson Laboratory, United States
Disclosure(s):
Luke Trinity, PhD: No financial relationships to disclose
Introduction/Rationale: Cytomegalovirus (CMV) is a common herpesvirus that establishes lifelong latency and becomes increasingly prevalent with age.
Methods: We systematically characterized CMV-associated immune remodeling by analyzing six human cohorts (two newly built) using single-cell RNA sequencing, T cell receptor (TCR) sequencing, and flow cytometry.
Results: Beyond the well-known expansion of CD4⁺/CD8⁺ TEMRA, adaptive NK, and γδ T cells, CMV(+) adults exhibited increased frequencies of GZMK⁺ CD8⁺ T cells and atypical B cells, alongside a reduction of CD56dim NK cells. Longitudinal profiling of an individual who seroconverted revealed rapid CMV-driven shifts in circulating immune cell frequencies. Single-cell TCR data analyzed using a large database of CMV-associated clones combined with predictive modeling (CMVerify), identified novel CMV-specific clonal expansions reproducible across two independent cohorts. In the CD8⁺ lineage, CMV-specific clones were enriched in GZMK⁺ CD8⁺ and CD8⁺ TEMRA cells, while in the CD4⁺ lineage, Th1 cells showed clonal expansion alongside CD4⁺ TEMRA cells.
Conclusion: This integrative study revealed how latent CMV alters the cellular and clonal landscape, defining Th1 and GZMK⁺ CD8⁺ cells as newly recognized elements of the latent CMV response in humans.
