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* Graduate Program in Molecular Virology and Microbiology,
Graduate Program in Immunology,
Department of Ophthalmology,
Department of Immunology,
¶ Department of Molecular Genetics and Biochemistry, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15213; and
|| Department of Microbiology and Immunology, Milton S. Hershey Medical Center, Pennsylvania State University, College of Medicine, Hershey, PA 17033
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-
. 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- 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants 5T32 AI049820 (to M.L.F.), T32 AI060525 (to B.S.S.), AI49719 (to R.H.B.), EY05945, P30 EY08098 (to R.L.H.), an unrestricted grant from Research to Prevent Blindness (New York, NY), and the Eye and Ear Foundation of Pittsburgh.
2 Address correspondence and reprint requests to Dr. Robert L. Hendricks, Eye and Ear Institute, Room 922, 203 Lothrop Street, Pittsburgh, PA 15213. E-mail address: hendricksrr{at}upmc.edu
3 Abbreviations used in this paper: TG, trigeminal ganglia; gB, glycoprotein B; MFI, mean fluorescence intensity.
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