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 phosphorylation of a 95-kDa viral protein and dephosphorylation of 55- and 103-kDa cellular proteins during the course of BHV-1 infection. We demonstrated BHV-1 glycoprotein E (gE) to be the tyrosine phosphorylated viral protein by immunoprecipitation. Inhibition of phosphorylation of BHV-1 gE by tyrosine kinase inhibitors genistein and tyrphostin AG1478 substantially lowered the viral titer in Madin-Darby bovine kidney cells. The decrease in viral titer was directly proportional to the decrease in phosphorylation of the BHV-1 gE. Interestingly, these kinase inhibitors did not inhibit the replication of the BHV-1 gE deletion mutant virion (BHV-1gEDelta3.1). Our findings suggest that the wild-type BHV-1, with a functional gE protein, uses a different pathway of signaling events than the BHV-1 gE deletion mutant in replication. Our results indicate that the tyrosine phosphorylation of the cytoplasmic tail of BHV-1 gE is an important post-translational modification of the functional protein. An application of this study may be the use of tyrosine kinase inhibitors in controlling the BHV-1 infection.
Shaw
A M
AM
Department of Veterinary Science, South Dakota State University, Brookings, South Dakota, 57007, USA.
Braun
L
L
Frew
T
T
Hurley
D J
DJ
Rowland
R R
RR
Chase
C C
CC
D000818:Animals; D002213:Capsid / Q000378:metabolism; D002460:Cell Line; D004285:Dogs; D017353:Gene Deletion; D019833:Genistein / Q000494:pharmacology; D007242:Herpesvirus 1, Bovine / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism*; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines; D020032:Tyrphostins / Q000494:pharmacology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins; D014779:Virus Replication / Q000502:physiology*
D011799:Quinazolines; D020032:Tyrphostins; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C046998:bovine herpesvirus type-1 glycoproteins; C101044:RTKI cpd; D019000:Phosphotyrosine; D019833:Genistein; D011505:Protein-Tyrosine Kinases