Two mutations in gB-1 and gD-1 of herpes simplex virus type 1 are involved in the "fusion from without" phenotype in different cell types.

Previous studies have shown that certain strains of herpes simplex viruses type 1 (HSV-1) are able to induce "fusion from without" (FFWO) which means no transcription or translation of the viral genome happens. The main determinants for FFWO in BHK cells are mutations in the C-terminal part of gB-1. But single mutations in this part of the genome are not sufficient to transfer the FFWO phenotype also to Vero cells. Here, we report that FFWO of HSV strains indeed need additional mutations in the N-terminal part of gD in order to produce the FFWO phenotype in BHK and Vero cells. By marker transfer we are able to show that loss of mutations in the N-terminal part of gD influences the ability to induce FFWO in Vero cells but not in BHK cells. We assume that a mutated gD allows the entrance of a multiple number of virus particles into the cell and enhances therefore the fusion activity of the mutated gB. Mutations in gD alone are not sufficient for fusion activity of HSV.