Effect of (E)-5-(2-bromovinyl)-2'-deoxyuridine on synthesis of herpes simplex virus type 1-specific polypeptides.
The antiherpesvirus agent (E)-5-(2-bromovinyl)-2'-deoxyuridine caused marked alterations in the synthesis and processing of several herpes simplex virus type 1 (HSV-1)-infected-cell polypeptides. Analogous to other thymidine analogs, there was a dose-dependent decrease in several beta and gamma polypeptides and an accumulation of HSV-1 thymidine kinase. In contrast to the action of other thymidine analogs, there were alterations in alpha polypeptides, including an increase in the synthesis and phosphorylation of infected-cell polypeptide 4b and a decrease in the synthesis of infected-cell polypeptide 27. The phosphorylation of several other HSV-1 phosphoproteins was mildly inhibited. (E)-5-(2-Bromovinyl)-2'-deoxyuridine inhibited the glycosylation of the major HSV-1 glycoproteins, and this activity appeared to be independent of the incorporation of the drug into the viral DNA. Thus, the alterations in HSV-1 polypeptide expression appear to be due to the presence of the drug in a low-molecular-weight form as well as its presence in the viral DNA. This suggests that this analog or a phosphorylated derivative might act as an inhibitor of an enzyme(s) responsible for posttranslational modification of polypeptides.
D000818:Animals; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002522:Chlorocebus aethiops; D004279:DNA, Viral / Q000096:biosynthesis; D005944:Glucosamine / Q000096:biosynthesis; D006023:Glycoproteins / Q000096:biosynthesis; D008715:Methionine / Q000378:metabolism; D010452:Peptide Biosynthesis; D010750:Phosphoproteins / Q000096:biosynthesis; D018139:Simplexvirus / Q000378:metabolism*; D014764:Viral Proteins / Q000096:biosynthesis
D004279:DNA, Viral; D006023:Glycoproteins; D010750:Phosphoproteins; D014764:Viral Proteins; C020235:brivudine; D008715:Methionine; D001973:Bromodeoxyuridine; D005944:Glucosamine