Involvement of p32 and microtubules in alteration of mitochondrial functions by rubella virus

J Virol. 2011 Apr;85(8):3881-92. doi: 10.1128/JVI.02492-10. Epub 2011 Jan 19.

Abstract

The interaction of the rubella virus (RV) capsid (C) protein and the mitochondrial p32 protein is believed to participate in virus replication. In this study, the physiological significance of the association of RV with mitochondria was investigated by silencing p32 through RNA interference. It was demonstrated that downregulation of p32 interferes with microtubule-directed redistribution of mitochondria in RV-infected cells. However, the association of the viral C protein with mitochondria was not affected. When cell lines either pretreated with respiratory chain inhibitors or cultivated under (mild) hypoxic conditions were infected with RV, viral replication was reduced in a time-dependent fashion. Additionally, RV infection induces increased activity of mitochondrial electron transport chain complex III, which was associated with an increase in the mitochondrial membrane potential. These effects are outstanding among the examples of mitochondrial alterations caused by viruses. In contrast to the preferential localization of p32 to the mitochondrial matrix in most cell lines, RV-permissive cell lines were characterized by an almost exclusive membrane association of p32. Conceivably, this contributes to p32 function(s) during RV replication. The data presented suggest that p32 fulfills an essential function for RV replication in directing trafficking of mitochondria near sites of viral replication to meet the energy demands of the virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Electron Transport
  • Gene Silencing
  • Host-Pathogen Interactions*
  • Humans
  • Membrane Potential, Mitochondrial
  • Microtubules / metabolism*
  • Mitochondria / metabolism*
  • Mitochondria / virology*
  • Mitochondrial Proteins / antagonists & inhibitors
  • Mitochondrial Proteins / metabolism*
  • RNA Interference
  • Rubella virus / pathogenicity*
  • Viral Core Proteins / metabolism*

Substances

  • C1QBP protein, human
  • Mitochondrial Proteins
  • Viral Core Proteins
  • nucleocapsid protein (C), rubella virus