MECHANISM OF PH INDEPENDENT HSV ENTRY

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DESCRIPTION: The present proposal will explore the means by which herpes simplex virus type I (HSV-1) enters cells by pH independent mechanisms. The applicant previous discovered a cell line that is refractory to HSV-1 entry, but which can replicate HSV-1 when infectious DNA is transfected. Utilizing transfection with libraries of HeLa cDNA clones, a novel human gene, B5 was discovered in the applicant's laboratory. This clone is different from the recently discovered human HVEM gene. The studies outlined here will center on the characterization of this gene and its role as a receptor for viral entry. The specific aims of the project are: 1) to characterize the structure and tissue distribution of B5 and to prepare tools for functional analysis including stably transfected cell lines and antibodies; 2) to determine the function of B5 in HSV entry, spread and infection by assessing stable binding, penetration and un- coating during entry of HSV-1. Investigations will also be performed to determine if B5 influences HSV-1 spread, whether it interacts with ligands, and whether it associates with HVEM; 3) to examine if and how B5 interacts with viral and cellular proteins to mediate HSV entry and membrane fusion.