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.
Freeman
Michael L
ML
Graduate Program in Molecular Virology and Microbiology, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Sheridan
Brian S
BS
Bonneau
Robert H
RH
Hendricks
Robert L
RL
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D004279:DNA, Viral / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D018628:Gene Dosage; D006561:Herpes Simplex / Q000276:immunology / Q000473:pathology / Q000523:psychology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000276:immunology* / Q000821:virology; D012668:Trigeminal Ganglion / Q000276:immunology / Q000473:pathology / Q000821:virology; D014775:Virus Activation / Q000276:immunology; D017735:Virus Latency / Q000276:immunology*
D004279:DNA, Viral; D007371:Interferon-gamma