Psychological stress compromises CD8+ T cell control of latent herpes simplex virus type 1 infections

Recurrent HSV-1 ocular disease results from reactivation of latent virus in trigeminal ganglia, often following immunosuppression or exposure to a variety of psychological or physical stressors. HSV-specific CD8(+) T cells can block HSV-1 reactivation from latency in ex vivo trigeminal ganglia cultures through production of IFN-gamma. In this study, we establish that either CD8(+) T cell depletion or exposure to restraint stress permit HSV-1 to transiently escape from latency in vivo. Restraint stress caused a reduction of TG-resident HSV-specific CD8(+) T cells and a functional compromise of those cells that survive. Together, these effects of stress resulted in an approximate 65% reduction of cells capable of producing IFN-gamma in,response to reactivating virus. Our findings demonstrate persistent in vivo regulation of latent HSV-1 by CD8(+) T cells, and strongly support the concept that stress induces HSV-1 reactivation from latency at least in part by compromising CD8(+) T cell surveillance of latently infected neurons.