CD8+ T cell mediated control of HSV-1 Latency in TG

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Herpes Simplex Virus 1 (HSV-1) establishes a latent infection in sensory ganglia of the peripheral nervous system and reactivation of latent HSV-1 represents the most frequent cause of infectious encephalitis. In addition, experimental evidence suggests a possible link between latent infections of the nervous system and the etiology of neurodegenerative diseases. Our previous data demonstrate evidence that CD8+ T cells are required for preventing the reactivation of HSV-1 following the establishment of latency in trigeminal ganglia. While CD8+ T cells are effective in preventing reactivation in all latently infected neurons, IFNgamma (a principal effector molecule employed by CD8+ T cells) is capable of preventing HSV-1 reactivation in some, but not all neurons. Our preliminary work indicates that perforin and lytic granules (granzymes A and B) may be required for CD8+ T cells to prevent HSV-1 reactivation. We plan to investigate the role of perforin and lytic granules in CD8+ T cell control of HSV-1 latency, and the factors that determine the use of such machinery by CD8+ T cells. The understanding of viral/immune system interactions in this model may lead to modified strategies for vaccine development. [unreadable] [unreadable]