Critical Role of Regulatory T Cells in the Latency and Stress-Induced Reactivation of HSV-1

Herpes simplex virus 1 (HSV-1) spreads in populations through a latency entry and reactivation cycle. The role of host immune-suppressive factor regulatory T cells (Treg cells) in controlling latency establishment and reactivation is not completely understood. Here, using an HSV-1 ocular infection murine model, we observe a positive correlation between the level of Treg cells and viral infectivity and demonstrate the requirement for Treg cells in latency establishment. Furthermore, we show that host stress leads to HSV-1 reactivation via increased Treg cell control of CD8+ T cells, permitting viral replication under diminished immune surveillance. Together, we propose that Treg cell regulation may serve as a key target for controlling HSV infection.