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Stress Compromises HSV-1-Specific Immunity in Latently Infected Sensory Ganglia

Recurrent HSV-1 ocular disease results from reactivation of latent virus in trigeminal ganglia (TG), 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 TG cultures in part through production of IFN-&#947. Here we establish that either CD8+ T cell depletion or exposure to restraint stress permits HSV-1 to transiently escape from latency in vivo. Restraint stress caused a glucocorticoid-associated reduction of TG-resident HSV-specific CD8+ T cells, and a functional compromise of those cells that survive, at least partly mediated by catecholamines. Together, these effects of stress resulted in an approximate 65% reduction of cells capable of producing IFN-&#947, and impairment in the ability of those cells to release lytic granules, in response to reactivating virus. We also establish that restraint stress during the primary infection results in a 54% reduction of virus-specific IL-7R&#945+ memory precursor cells in the TG at the peak of expansion. When mice stressed early were stressed again during latency, their T cell response may be further compromised. 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.

Identiferoai:union.ndltd.org:PITT/oai:PITTETD:etd-12072007-123821
Date07 December 2007
CreatorsFreeman, Michael L
ContributorsJoAnne Flynn, PhD, Bruce Rabin, MD, PhD, Paul Kinchington, PhD, Robert Hendricks, PhD, Jon Piganelli, PhD
PublisherUniversity of Pittsburgh
Source SetsUniversity of Pittsburgh
LanguageEnglish
Detected LanguageEnglish
Typetext
Formatapplication/pdf
Sourcehttp://etd.library.pitt.edu/ETD/available/etd-12072007-123821/
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