Axin expression enhances herpes simplex virus type 1 replication by inhibiting virus-mediated cell death in L929 cells

J Gen Virol. 2013 Jul;94(Pt 7):1636-1646. doi: 10.1099/vir.0.051540-0. Epub 2013 Mar 27.


Herpes simplex virus type 1 (HSV-1) replicates in various cell types and induces early cell death, which limits viral replication in certain cell types. Axin is a scaffolding protein that regulates Wnt signalling and participates in various cellular events, including cellular proliferation and cell death. The effects of axin expression on HSV-1 infection were investigated based on our initial observation that Wnt3a treatment or axin knockdown reduced HSV-1 replication. L929 cells expressed the axin protein in a doxycycline-inducible manner (L-axin) and enhanced HSV-1 replication in comparison to control cells (L-EV). HSV-1 infection induced cell death as early as 6 h after infection through the necrotic pathway and required de novo protein synthesis in L929 cells. Subsequent analysis of viral protein expression suggested that axin expression led to suppression of HSV-1-induced premature cell death, resulting in increased late gene expression. In analysis of axin deletion mutants, the regulators of the G-protein signalling (RGS) domain were involved in the axin-mediated enhancement of viral replication and reduction in cell death. These results suggest that viral replication enhancement might be mediated by the axin RGS domain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axin Protein / genetics
  • Axin Protein / metabolism*
  • Axin Protein / pharmacology
  • Cell Death / drug effects*
  • Chlorocebus aethiops
  • Herpesvirus 1, Human / pathogenicity
  • Herpesvirus 1, Human / physiology
  • L Cells
  • Mice
  • Vero Cells
  • Virus Replication / drug effects*


  • Axin Protein
  • Axin1 protein, mouse