Inhibition of Theiler's virus-induced apoptosis in infected murine macrophages results in necroptosis

Virus Res. 2015 Jan 2:195:177-82. doi: 10.1016/j.virusres.2014.10.017. Epub 2014 Oct 27.

Abstract

In mice Theiler's murine encephalomyelitis virus (TMEV) persists in macrophages that eventually undergo apoptosis. TMEV infection of macrophages in culture induces apoptosis through the intrinsic pathway, restricting virus yields. We show that inhibition of TMEV-induced apoptosis leads to phosphorylation of receptor interacting protein 1 (RIP1), localization of RIP1 and RIP3 to mitochondria, ROS production independent of MAPK activation and programmed necrosis (necroptosis). Blocking both apoptosis and necroptosis restored virus yields.

Keywords: Apoptosis; Necroptosis; RIP1; Theiler's virus; Virus titers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death*
  • GTPase-Activating Proteins / metabolism
  • Host-Pathogen Interactions*
  • Macrophages / physiology*
  • Macrophages / virology*
  • Mice
  • Mitochondria / chemistry
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Reactive Oxygen Species / metabolism
  • Receptor-Interacting Protein Serine-Threonine Kinases / metabolism
  • Theilovirus / physiology*
  • Viral Load

Substances

  • GTPase-Activating Proteins
  • Ralbp1 protein, mouse
  • Reactive Oxygen Species
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Ripk3 protein, mouse