Herpes simplex virus 1 protein kinase is encoded by open reading frame US3 which is not essential for virus growth in cell culture

Abstract

Earlier reports have described a novel protein kinase in cells infected with herpes simplex or pseudorabies viruses. These novel enzymes were characterized by their acceptance of protamine as a substrate and by their differential chromatographic behavior in anion-exchange chromatography. We report that this activity was not present in extracts of uninfected cells or of cells infected with a mutant constructed so as to contain a deletion in the US3 open reading frame mapping in the small component of herpes simplex virus 1 DNA. The activity was present in extracts of cells infected with wild-type virus and with a recombinant in which the US3 open reading frame had been rescued. Our results are consistent with the observation reported earlier that the coding sequences predict an amino acid motif common to protein kinases and lead to the conclusion that the US3 open reading frame encodes-a virus-specific protein kinase that is not required for virus growth in cells in culture.

Protein Kinase B/Akt Is Present in Activated Form throughout the Entire Replicative Cycle of ΔUS3 Mutant Virus but Only at Early Times after Infection with Wild-Type Herpes Simplex Virus 1

“…The antiapoptotic functions identified to date map to glycoprotein D (48), glycoprotein J (17,18,48), the protein kinase encoded by the U S 3 gene (24,25,37), and the viral ribonucleotide reductase (33). The U S 3 protein kinase, the focus of this and several preceding reports (4,5,8,9,15,17,25,29,30,32,34,37,39), is a multifunctional protein. The three major functions associated with this kinase are the disruption of nuclear lamina to enable egress of capsids from nuclei (39), phosphorylation of histone-deacetylating enzymes 1 and 2 (35), and blocking apoptosis induced by viral gene products or exogenous agents (5,8,9,17,25,29,30,32).…”

“…Earlier studies from this and other laboratories have shown that cells infected with wild-type herpes simplex virus 1 (HSV-1) are protected against apoptosis induced by a number of exogenous agents as well as by replication-incompetent mutants lacking the regulatory genes ␣4 and/or ␣27 (13,14,18,22,24). The antiapoptotic functions identified to date map to glycoprotein D (48), glycoprotein J (17,18,48), the protein kinase encoded by the U S 3 gene (24,25,37), and the viral ribonucleotide reductase (33). The U S 3 protein kinase, the focus of this and several preceding reports (4,5,8,9,15,17,25,29,30,32,34,37,39), is a multifunctional protein.…”

Expression of herpes simplex virus type 2 US3 affects the Cdc42/Rac pathway and attenuates c‐Jun N‐terminal kinase activation

“…At least three (US3, UL13 and Nterminal domain of the UL39) HSV genes encode protein kinases (PK). Among them, the US3 was first identified as an HSV-specific serine/threonine-protein kinase (Frame et al 1987;Purves et al 1987;Daikoku et al 1993). The US3 PK of HSV-2 has an apparent molecular mass of 66 kDa and appears to have autophosphorylation activity.…”

UL13 Protein Kinase of Herpes Simplex Virus 1 Complexes with Glycoprotein E and Mediates the Phosphorylation of the Viral Fc Receptor: Glycoproteins E and I

“…Herpes simplex virus 1 (HSV-1) encodes two protein kinases specified by the U L 13 and U S 3 genes (Coulter et al, 1993;Cunningham et al, 1992;Daikoku et al, 1997;Frame et al, 1987;Overton et al, 1992;Purves and Roizman, 1992;Purves et al, 1986aPurves et al, ,b, 1987. The kinase specified by the U L 13 gene is of particular interest since the protein is packaged in the tegument, a structural component of the virion located between the capsid and the envelope (Coulter et al, 1993;Cunningham et al, 1992;Overton et al, 1992) and indeed, a protein kinase activity is associated with purified capsid±tegument structures (Lemaster and Roizman, 1980).…”