Functional interactions between herpes simplex virus pUL51, pUL7 and gE reveal cell-specific mechanisms for epithelial cell-to-cell spread.

Herpes simplex virus spread between epithelial cells is mediated by virus tegument and envelope protein complexes including gE/gI and pUL51/pUL7. pUL51 interacts with both pUL7 and gE/gI in infected cells. We show that amino acids 30-90 of pUL51 mediate interaction with pUL7. We also show that deletion of amino acids 167-244 of pUL51, or ablation of pUL7 expression both result in failure of gE to concentrate at junctional surfaces of Vero cells. We also tested the hypothesis that gE and pUL51 function on the same pathway for cell-to-cell spread by analyzing the phenotype of a double gE/UL51 mutant. In HaCaT cells, pUL51 and gE function on the same spread pathway, whereas in Vero cells they function on different pathways. Deletion of the gE gene strongly enhanced virus release to the medium in Vero cells, suggesting that the gE-dependent spread pathway may compete with virion release to the medium.