Inhibition of herpes simplex virus type 2 (HSV-2) viral replication by the dominant negative mutant polypeptide of HSV-1 origin binding protein

Abstract

UL9-C535C, the trans-dominant negative mutant polypeptide of herpes simplex virus type 1 (HSV-1) UL9 origin binding protein, is a potent inhibitor of HSV-1 viral DNA replication. This study focused on testing whether HSV-1 UL9-C535C and a genetically engineered UL9-C535C-encoding HSV-1 recombinant virus CJ83193 could inhibit herpes simplex virus type 2 (HSV-2) infection. First, a stable cell line, R-C535C, expressing a high level of UL9-C535C in the presence of tetracycline and little or no UL9-C535C in the absence of tetracycline was established. The single step growth experiment showed that like HSV-1, the de novo synthesis of HSV-2 could be suppressed ∼1000-fold by UL9-C535C expressed in R-C535C cells in the presence of tetracycline. Secondly, compared with cells singly infected with HSV-2, co-infection of Vero cells with HSV-2 and CJ83193 reduced the replication efficiency of HSV-2 in co-infected cells by 30–40 fold in a single-step growth assay, which coincided with marked reduction in viral late gene expression, but not the expression of viral immediate-early genes. Taken together, in view of our recent demonstration that CJ83193 can serve as an effective vaccine in preventing HSV-1 infection in mice, one can generate a CJ83193-like HSV-2 recombinant virus that could potentially function as a new therapeutic class of recombinant viral vaccine against HSV-2 infection.