ARTICLE ABSTRACT
								DOI: 10.1099/vir.0.19128-0
								Online 25 March 2003

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

Stefan Finke, Roland Mueller-Waldeck and Karl-Klaus Conzelmann

Max von Pettenkofer Institute and Gene Center, Ludwig Maximilians University Munich, Feodor Lynen Str. 25, D-81377 Munich, Germany

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.

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© 2003 SGM

This article is now available in the June 2003 print issue of JGV (vol. 84, 1613–1621). The complete issue of the journal may be seen in electronic form on JGV Online.