The interaction of human herpes simplex virus (HSV) with the host cell may result in one or more cell-virus interactions including cytocidal infection, latent infection, and cellular transformation. One of the most extensively documented processes associated with HSV infection is virus latency. HSV has a propensity to exist in humans and experimental animals without signs of overt clinical disease. The potential role of latent HSV infection in viral oncogenesis is an area of intense current interest. The central objective of this proposal is to use an in vitro model system for HSV latency to analyze the state of the virus genome during establishment and maintenance of the latent state and during reactivation of virus synthesis. Scientific disciplines involved include those of oncology, virology, neurology, molecular biology, cell biology, genetics and cell culture. These studies will involve characterization of the latent HSV genome by a variety of techniques including in situ hybridization and Southern and Northern blotting procedures. The virus gene functions(s) involved in establishment and maintenance of the latent state and the virus reactivation process will be characterized by delivery of virus recombinant DNA molecules and virus gene products to latently infected cells by either transfection or polyethylene glycol-mediated bacterial protoplast fusion. These studies are health-related because they deal with ubiquitous viruses found throughout the animal kingdom, including HSV and HCMV. These viruses are known to cause latent infection in their natural host and to induce oncogenic transformation in in vitro and in vivo. Their association with a number of human neoplasms, including cervical carcinoma and Kaposi sarcoma, has been well documented: some of these tumors have been shown to carry partial genomes of viruses to be studied. Ultimately, these studies should enable better understanding of how herpesviruses cause latent and chronic infections and cancer. Information being obtained in this project may aid in the provision of a means for early diagnosis, for cure, or ultimately, for prevention of the many diseases caused by these viruses.
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