Disruption of the varicella-zoster virus dUTPase and the adjacent ORF9A gene results in impaired growth and reduced syncytia formation in vitro

Virology. 1997 Aug 4;234(2):186-95. doi: 10.1006/viro.1997.8652.


Varicella-zoster virus (VZV) open reading frame 8 (ORF8) is predicted to encode the viral dUTPase and the adjacent gene, ORF9A, is thought to encode a membrane protein homologous to HSV-1 UL49.5. A fusion protein, in which the amino portion of glutathione-S-transferase was fused to amino acids 5 to 396 of VZV ORF8 protein, had dUTPase activity in vitro. Construction of a mutant VZV with stop codons or a deletion in the ORF8 gene resulted in loss of viral dUTPase activity. Antibody to VZV ORF9A protein demonstrated a 7-kDa protein located in the membranes of virus-infected cells. Insertion of stop codons into VZV ORF9A resulted in VZV that produced smaller plaques than parental virus. Inactivation of both VZV ORF8 and ORF9A resulted in a virus that grew to lower titers and was impaired for syncytia formation when compared to parental virus. In contrast, a similar mutation in HSV-1 has no effect on growth of the virus in vitro. These results identify loci in the VZV genome that are required for a syncytial phenotype in vitro.

MeSH terms

  • Gene Deletion
  • Gene Expression Regulation, Viral*
  • Genes, Viral*
  • Genome, Viral*
  • Herpesvirus 3, Human / enzymology
  • Herpesvirus 3, Human / genetics*
  • Herpesvirus 3, Human / growth & development
  • Pyrophosphatases / genetics*
  • Recombinant Fusion Proteins / genetics


  • Recombinant Fusion Proteins
  • Pyrophosphatases
  • dUTP pyrophosphatase