Post entry roles of nectin-1 in HSV replication

Northwestern University At Chicago, Evanston IL

Investigators

Abstract

[unreadable] DESCRIPTION (provided by applicant): The precise role of entry receptors in the pathogenesis of HSV infections is not well understood. The objective of this research project is to understand the molecular mechanisms involved in cell-cell spread of HSV infection. The hypothesis of this study is that interaction of viral ligand, glycoprotein D (gD), and its receptor, nectin-1 but not HVEM is required for cell-cell spread of HSV infection. This hypothesis, supported by strong preliminary data, will be tested by two approaches: (a) recombinant HSV strains unable to interact with nectin and (b) cell lines that will produce the mutant gD proteins unable to interact with nectin-1 will be used to assess the post entry events in viral replication and cell-cell spread. This research is innovative because it will evaluate for the first time that the effects of gD:nectin interaction on post-entry events in HSV replication and cell-cell spread. The significance of the proposed study is that it aims at identifying the factors that can inhibit the process of latency achieved by herpes simplex viruses to cause life-long infection in the human population. This research may also identify potential live viral vaccine candidates for the prevention of primary and recurrent HSV disease. [unreadable] [unreadable] [unreadable]