Inhibition of herpes simplex virus type 2 (HSV-2) viral replication by the dominant negative mutant polypeptide of HSV-1 origin binding protein.
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 approximately 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.
Yao
Feng
F
Laboratory of Wound Repair and Gene Transfer, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. fyao@rics.bwh.harvard.edu
Eriksson
Elof
E
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001483:Base Sequence; D002460:Cell Line; D002522:Chlorocebus aethiops; D004261:DNA Replication / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000494:pharmacology*; D005786:Gene Expression Regulation; D005799:Genes, Dominant; D006558:Herpes Genitalis / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011995:Recombination, Genetic; D013752:Tetracycline / Q000494:pharmacology; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D004268:DNA-Binding Proteins; D014764:Viral Proteins; C064565:UL9 protein, Human herpesvirus 1; D013752:Tetracycline