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R.L. Hendricks, M.L. Freeman, R.H. Bonneau; Stress–Induced Dysregulation of HSV–Specific Immunity in Latently–Infected Sensory Ganglia . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4301.
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© ARVO (1962-2015); The Authors (2016-present)
Recurrent herpes simplex virus type 1 (HSV–1)–induced keratitis results from reactivation of latent virus in the trigeminal ganglion (TG). We have shown that HSV gB498–505 –specific CD8+ T cells can block HSV–1 reactivation from latency. Here we examine the role of psychological stress in dysregulation of virus–specific CD8+ T cell number, function, and ability to prevent viral reactivation from latency.
Male C57BL/6 mice were infected with HSV–1 via corneal scarification and viral latency was established in the trigeminal ganglia (TG). At day 30 post infection, mice were subjected to four consecutive nights of 12–hour restraint sessions (a psychological stressor). TG were excised, dissociated, and examined for CD8+ T cell numbers, phenotype, and functionality. Viral reactivation was assessed by real–time PCR and in an ex vivo culture system.
Restraint stress results in a transient decrease in the number of virus–specific CD8+ T cells in the TG. CD8+ T cell production of IFNγ is impaired in response to latently–infected neurons in vivo and ex vivo, but not when optimally stimulated with gB–pulsed targets. Stress does not impair the CD8+ T cell ability to degranulate, and storage of granzyme B in lytic granules is enhanced. Stress–induced changes in CD8+ T cell function are followed by an increase in viral DNA copy number in the TG, and reactivation is accelerated in ex vivo TG cultures.
Restraint stress promotes HSV–1 reactivation from latency in part by dysregulating the virus–specific CD8+ T cell response in the TG.
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