The rubella virus capsid protein inhibits mitochondrial import

Carolina S Ilkow1, Daniel Weckbecker, Woo Jung Cho

  • 1Department of Cell Biology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.

Journal of Virology
|October 23, 2009
PubMed

Insights

The rubella virus (RV) capsid protein binds to mitochondria and inhibits the import of proteins, impacting mitochondrial function. This viral protein affects a conserved mitochondrial import pathway, representing a novel viral mechanism.

Area of Science:

  • Virology
  • Cell Biology
  • Mitochondrial Biology

Background:

  • The rubella virus (RV) capsid protein is known to be involved in viral assembly at the Golgi complex.
  • Unexpectedly, RV capsid protein also associates with mitochondria, a location not directly related to viral replication.
  • The functional significance of this mitochondrial localization of RV capsid remains unclear.

Purpose of the Study:

  • To investigate the interaction between rubella virus capsid protein and mitochondria.
  • To determine if RV capsid protein affects mitochondrial protein import and processing.
  • To elucidate the mechanism by which RV capsid protein influences mitochondrial function.

Main Methods:

  • In vitro assays to assess the effect of RV capsid on mitochondrial precursor protein import.
  • Analysis of intramitochondrial protein levels in RV-infected cells.
  • Cross-species mitochondrial import assays (mammalian and yeast).
  • Site-directed mutagenesis of the RV capsid protein.

Main Results:

  • Rubella virus capsid protein was shown to inhibit the in vitro import and processing of mitochondrial precursor proteins.
  • RV-infected cells exhibited reduced levels of the mitochondrial matrix protein p32.
  • Capsid protein blocked protein import into both mammalian and yeast mitochondria, indicating a conserved target.
  • Mutations in the N-terminal arginine residues of capsid abolished its inhibitory effect on mitochondrial protein import, despite retaining mitochondrial binding.

Conclusions:

  • Rubella virus capsid protein directly interferes with the mitochondrial protein import machinery.
  • This interference affects a conserved component of the protein translocation apparatus.
  • The N-terminal arginine residues of the capsid protein are critical for its ability to inhibit mitochondrial import.
  • This study reports the first instance of a viral protein impacting mitochondrial protein import, revealing a novel mechanism of viral pathogenesis.

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