The HSV-1 Us3 protein kinase is sufficient to block apoptosis induced by overexpression of a variety of Bcl-2 family members

Virology. 2004 Feb 20;319(2):212-24. doi: 10.1016/j.virol.2003.10.019.

Abstract

The Us3 protein kinase encoded by herpes simplex virus type-1 (HSV-1) suppresses apoptosis in infected cells and is sufficient to block apoptosis induced by overexpression of Bad [Proc. Natl. Acad. Sci. 98 (2001) 10410]. While Us3 can induce phosphorylation of Bad, phosphorylation of Bad is dispensable for Us3 anti-apoptotic function [J. Virol. 77 (2003) 6567]. We extend the findings with Bad to demonstrate that Us3 blocks apoptosis induced by overexpression of Bid, a factor parallel to Bad in the apoptotic pathway, and Bax, a factor downstream of Bad in the apoptotic pathway. A previous report suggested that Us3 exerts its effects at a premitochondrial stage [J. Virol. 75 (2001) 5491], but our results suggest that Us3 exerts anti-apoptotic effects downstream of the mitochondria. We show that the kinase activity of Us3 is necessary for Us3 anti-apoptotic effects, because a catalytically inactive form of Us3 was unable to block apoptosis. A second function of Us3, primary envelopment during viral egress, is conserved in the Us3 homologue of Pseudorabies virus (PRV) [J. Gen. Virol. 82 (2001) 2363]. Experiments published here demonstrate that PRV Us3 can also block apoptosis induced by Bax, suggesting that the anti-apoptotic activity of Us3 is conserved across alpha-herpesviruses.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis*
  • Cell Line
  • Cell Line, Tumor
  • Herpesvirus 1, Human / enzymology
  • Herpesvirus 1, Human / physiology*
  • Herpesvirus 1, Suid / enzymology
  • Herpesvirus 1, Suid / physiology
  • Humans
  • Mitochondria / metabolism
  • Mutation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Protein-Serine-Threonine Kinases / physiology*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Transfection
  • Viral Proteins
  • bcl-2-Associated X Protein

Substances

  • BAX protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Viral Proteins
  • bcl-2-Associated X Protein
  • Protein-Serine-Threonine Kinases
  • US3 protein, Human herpesvirus 1