Differentiation of multiple domains in the herpes simplex virus 1 protease encoded by the UL26 gene.

Abstract

Previous studies have shown that the herpes simplex virus 1 gene UL26 encodes a 635-amino acid protease that cleaves approximately 20 amino acids from the carboxyl terminus of itself and of a 329-amino acid product of the UL26.5 gene. The results of studies with a variety of protease inhibitors showed that the UL26 protease was inhibited by serine protease inhibitors but not by inhibitors of cysteine protease, aspartic acid protease, or metalloprotease. Mutations resulting in amino acid substitutions, deletions, or insertion of stop codons in the gene or of 20-amino acid stretches into the protease have delineated the dispensable domains I and IV at the amino and carboxyl domains of the gene product. The essential carboxyl-proximal domain (III) can be separated from the essential amino-proximal domain (II) by at least 20 amino acids. The amino-proximal domain is the most conserved region among varicella-zoster virus and human cytomegalovirus homologues of UL26. Of the conserved aspartic acid, histidine, or serine amino acids in this domain, only histidine-61 and -148 could not be replaced without impairment of the proteolytic activity.