Calmodulin controls the tempo of HSV-1 gene-expression cascade to reshape infection heterogeneity

Viral replication exhibits substantial heterogeneity among individual cells. Although temporally ordered gene-expression cascades are thought to contribute to such heterogeneity in DNA viruses, whether and how their tempo is regulated, and how cell-to-cell variability shapes population-level infection outcomes, remain unknown. Here, we developed a high-throughput live-cell imaging platform to track HSV-1 gene-expression dynamics in individual cells and, in combination with single-cell RNA sequencing, identified calmodulin (CaM) as a host regulator of HSV-1 gene-expression tempo. CaM accelerates progression from immediate-early to early and late phases at the single-cell level by advancing th