ROLE OF HERPESVIRUS COMPLEMENT-BINDING GLYCOPROTEIN

The applicant plans to pursue a career in academic medicine and biomedical research in the field of pediatric infectious diseases. The long-term objective of the training program is for the applicant to develop expertise in the field of molecular virology with particular attention to the interactions of viruses with the immune system as a basis for development of independent investigations. These skills will be necessary to fully answer fundamental clinical questions such as the role of viruses in oncogenesis and means of preventing the devastating effects of viral infections in the immunocompromised host. The specific training program planned includes course work in virology, molecular biology, and immunology during phase I. the aims of the research plan during phase I focus on the herpes simplex virus glycoprotein termed gC and its importance in viral adsorption. This glycoprotein is of special interest, in part because it is known to bid directly to a human complement protein and to interact with the complement cascade. Thus it offers a unique opportunity to examine the interactions among the virus, target cells, and the hot immune system, interactions that are undoubtedly important in viral pathogenesis. By comparing various gC mutant viral strains with wild-type virus in adsorption and infectivity assays, the biologic function of gC will be defined. In phase II of the study, the effects of complement-binding on viral adsorption and infectivity will be assessed. The knowledge gained from these studies will help further formulate theories on viral infectivity and may lead to promising new treatment modalities in the management of herpesvirus infections.