A role for bovine herpesvirus 1 (BHV-1) glycoprotein E (gE) tyrosine phosphorylation in replication of BHV-1 wild-type virus but not BHV-1 gE deletion mutant virus

Bovine herpesvirus 1 (BHV-1), an alphaherpesvirus, is a major pathogen that causes respiratory and reproductive infections. We observed tyrosine phosp horylation of a 95-kDa viral protein and dephosphorylation of 55- and 103-k Da cellular proteins during the course of BHV-1 infection. We demonstrated BHV-1 glycoprotein E (gE) to be the tyrosine phosphorylated viral protein b y immunoprecipitation. Inhibition of phosphorylation of BHV-1 gE by tyrosin e kinase inhibitors genistein and tyrphostin AG1478 substantially lowered t he viral titer in Madin-Darby bovine kidney cells. The decrease in viral ti ter was directly proportional to the decrease in phosphorylation of the BHV -1 gE. Interestingly, these kinase inhibitors did not inhibit the replicati on of the BHV-1 gE deletion mutant virion (BHV-1gE Delta 3.1). Our findings suggest that the wild-type BHV-1, with a functional gE protein, uses a dif ferent pathway of signaling events than the BHV-1 gE deletion mutant in rep lication. Our results indicate that the tyrosine phosphorylation of the cyt oplasmic tail of BHV-1 gE is an important post-translational modification o f the functional protein. An application of this study may be the use of ty rosine kinase inhibitors in controlling the BHV-1 infection. (C) 2000 Acade mic Press.