Inhibitory effect of tyrphostin on the replication of herpes simplex virus type 1.
Tyrphostins 9 and 47, inhibitors of protein-tyrosine kinase, inhibited the replication of herpes simplex virus type 1 (HSV-1), whereas tyrophostin 1, which does not inhibit protein-tyrosine kinase, did not affect the replication of HSV-1. The inhibitory effect of tyrphostin 9 was more potent than that of tyrphostin 47, and the IC50 of tyrphostin 9 was 40 nM. Sodium orthovanadate, an inhibitor of protein phosphotyrosine phosphatase, increased HSV-1 plaque formation and its effect was partly reversed by tyrphostin 9. The phosphorylation of viral phosphoproteins was decreased by tyrphostin 9 in a dose-dependent manner, but the tyrphostin 9-induced reduction of protein synthesis was not dose-dependent. At the late stage of infection, tyrosine phosphorylation was demonstrated in HSV-1 phosphoproteins. These results indicate that protein-tyrosine kinase is involved in the replication of HSV-1 and that tyrphostin can inhibit the synthesis and post-translational phosphorylation of the viral proteins.
Yura
Y
Y
Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, Japan.
Kusaka
J
J
Kondo
Y
Y
Tsujimoto
H
H
Yoshida
H
H
Sato
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D002522:Chlorocebus aethiops; D004261:DNA Replication / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009570:Nitriles / Q000494:pharmacology*; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation; D019000:Phosphotyrosine; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000276:immunology; D020032:Tyrphostins; D014638:Vanadates / Q000494:pharmacology; D014709:Vero Cells; D014764:Viral Proteins / Q000096:biosynthesis / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D009570:Nitriles; D010636:Phenols; D020032:Tyrphostins; D014764:Viral Proteins; C060152:tyrphostin 47; D019000:Phosphotyrosine; D014638:Vanadates; D014443:Tyrosine; C001784:SF 6847; D011505:Protein-Tyrosine Kinases