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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA034479-03
Application #
3172205
Study Section
Virology Study Section (VR)
Project Start
1983-06-01
Project End
1986-05-31
Budget Start
1985-06-01
Budget End
1986-05-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
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Wrzos, H; Gibbons, J; Abt, P L et al. (1990) Human herpesvirus 6 in monocytes of transplant patients. Lancet 335:486-7
Wrzos, H; Abt, P L; Rapp, F (1990) Anti-interferon antibody inhibits natural killer cell activity in HSV-2 genital infection in C57BL/6J mice. Intervirology 31:230-40
Nsiah, Y A; Tolman, R L; Karkas, J D et al. (1990) Suppression of herpes simplex virus type 1 reactivation from latency by (+-)-9-([(Z)-2-(hydroxymethyl)cyclohexyl]methyl) guanine (L-653,180) in vitro. Antimicrob Agents Chemother 34:1551-5
Shiraki, K; Rapp, F (1989) Protein analysis of herpes simplex virus latency in vitro established with cycloheximide. Virology 172:346-9
Cockley, K D; Rapp, F (1989) Analysis of viral proteins in human cytomegalovirus-infected cells during impaired lytic replication of herpes simplex virus. Virology 170:268-72
Scheck, A C; Wigdahl, B; Rapp, F (1989) Transcriptional activity of the herpes simplex virus genome during establishment, maintenance, and reactivation of in vitro virus latency. Intervirology 30:121-36
Shiraki, K; Rapp, F (1988) Effects of caffeine on herpes simplex virus. Intervirology 29:235-40
Cockley, K D; Shiraki, K; Rapp, F (1988) A human cytomegalovirus function inhibits replication of herpes simplex virus. J Virol 62:188-95

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