title: Cytomegalovirus protein substrates are not cleaved by the herpes simplex virus type 1 proteinase.
abstract: The herpesvirus maturational proteinase, assemblin, is made as a precursor that undergoes at least two autoproteolytic cleavages--one in a sequence toward its carboxyl end, called the maturational (M) site, and one in a sequence toward its midpoint, called the release (R) site. The M- and R-site sequences are both well conserved among the herpesvirus proteinase homologs, suggesting that the proteinase of one herpesvirus might be able to cleave the substrates of another. To test this possibility, we cloned and expressed in human cells the long (i.e., full-length open reading frame of proteinase gene) and short (i.e., proteolytic domain, assemblin) forms of the proteinase from human and simian cytomegalovirus (HCMV and SCMV, respectively) and from herpes simplex virus type 1 (HSV-1), as well as the genes for their respective assembly protein precursor substrates. Data from cotransfections of these proteinase genes with appropriate homologous and heterologous substrates showed that although the SCMV and HCMV enzymes cleaved the M-sites of the assembly protein substrates of all three viruses and an SCMV R-site substrate, the HSV-1 proteinase cleaved only its own substrate. This finding demonstrates that the substrate specificity properties of the HSV-1 enzyme differ from those of the two CMV enzymes.
authors.affiliation: Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: A R
authors.initials: AR
authors.lastname: Welch
authors.forename: E C
authors.initials: EC
authors.lastname: Villarreal
authors.forename: W
authors.initials: W
authors.lastname: Gibson
mesh_terms: D000595:Amino Acid Sequence; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000201:enzymology / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000201:enzymology*; D006801:Humans; D006868:Hydrolysis; D008969:Molecular Sequence Data; D012697:Serine Endopeptidases / Q000378:metabolism*; D013379:Substrate Specificity; D014764:Viral Proteins
chemical_list: D014764:Viral Proteins; C079287:scaffold protein, Herpes simplex virus-1; D010450:Endopeptidases; D012697:Serine Endopeptidases; C071910:assemblin