Rabies virus matrix protein regulates the balance of virus transcription and replication

J Gen Virol. 2003 Jun;84(Pt 6):1613-1621. doi: 10.1099/vir.0.19128-0.


RNA synthesis by negative-strand RNA viruses (NSVs) involves transcription of subgenomic mRNAs and replication of ribonucleoprotein complexes. In this study, the envelope matrix (M) protein of rabies virus (RV) was identified as a factor which inhibits transcription and stimulates replication. Transcription, but not replication, of RV minigenomes or of full-length RV was decreased by expression of heterologous M. Since RV assembly involving M and the glycoprotein G renders virus synthetically quiescent, an RV was generated with the M and G genes substituted by placeholders. Surprisingly, RNA synthesis by this recombinant was characterized not only by an increased transcription rate but also by a diminished accumulation of replication products. This phenotype was reversed in a dose-dependent manner by providing M in trans, showing that M is a replication-stimulatory factor. The role of M in determining the balance of replication and transcription was further exploited by generation of a recombinant RV with attenuated M expression, which is highly active in transcription. Regulation of RNA synthesis by matrix proteins may represent a general mechanism of nonsegmented NSVs, which is probably obscured by the silencing activity of M during virus assembly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cricetinae
  • Gene Expression
  • Gene Silencing
  • Genome, Viral
  • RNA, Viral / biosynthesis
  • RNA, Viral / genetics
  • Rabies virus / genetics*
  • Rabies virus / physiology*
  • Transcription, Genetic
  • Viral Matrix Proteins / genetics*
  • Viral Matrix Proteins / physiology*
  • Virus Replication


  • RNA, Viral
  • Viral Matrix Proteins