Gene expression analysis of HSV-1 infected cells

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DESCRIPTION (provided by applicant): Herpes simplex virus type 1 (HSV-1) is a human pathogen responsible for diseases such as orofacial lesions, keratoconjunctivitis, and encephalitis. Following primary infection at a peripheral site, the virus establishes latency in sensory neurons. Reactivation of latent virus results in recurrent herpetic disease. The focus of this research is to examine the effects of HSV-1 infection on cellular processes that could impact the success or failure of HSV-1 infection. Utilizing DMA microarrays to identify genes and pathways transcriptionally altered by viral infection, we will characterize the roles these cellular pathways have in infection, and how the virus evades or modifies the cellular response. Our current research focuses on an in vivo model of infection. In addition, an HSV-1 mutant lacking ICP34.5 will be included to compare the cellular response to a virus that is severely attenuated in mouse corneas. Our preliminary results from infected corneas show numerous virus-type specific changes, most notable that the mutant virus induces few changes in cellular gene expression at 3 dpi, and shows a decreased induction of the host immune response. We plan to compare viral replication and spread and the host immune response in mouse corneas, in order to construct a paradigm of the viral life cycle and host response in the corneal model. Herpes simplex viruses frequently cause a variety of syndromes from cold sores and genital sores, to more serious blinding ocular diseases, and potentially fatal brain infections. The virus is resistant to cure, and continues to cause severe problems despite the availability of antiviral drugs. This work will allow a better understanding of how the virus causes disease, and will pave the way towards improved therapies and vaccines against this significant pathogen.