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J Gen Virol 87 (2006), 3631-3636; DOI 10.1099/vir.0.81809-0

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© 2006 Society for General Microbiology

Short Communication

Mutations in the palm region of a plus-strand RNA virus polymerase result in attenuated phenotype

Andreas Gallei, Simone Widauer, Heinz-Jürgen Thiel and Paul Becher

Institut für Virologie (FB Veterinärmedizin), Justus-Liebig-Universität, Frankfurter Straße 107, D-35392 Giessen, Germany

Correspondence
Paul Becher
Paul.Becher{at}vetmed.uni-giessen.de

The three-dimensional structure of RNA-dependent RNA polymerases (RdRps) is highly conserved among RNA viruses. In a previous study, a unique set of mutant strains of Bovine viral diarrhea virus was obtained, encompassing either a genomic deletion of six codons or duplications of between 1 and 45 codons; these mutations affect different parts of the palm region, the most conserved part of RdRps containing the catalytic centre. In the present study, a detailed characterization of the RdRp mutant viruses was performed, demonstrating different degrees of a small-plaque phenotype in cell culture, correlating with significantly reduced viral RNA synthesis and delayed virus replication. Taken together, the results of this study demonstrate a surprising flexibility within the palm region of a plus-strand RNA virus RdRp, resulting in viral attenuation in vitro. This interesting insight into an essential viral protein may have implications for the development of vaccines and attenuated viral vectors.

Supporting material and a supplementary figure showing RT-PCR analyses of total RNA derived from cell-culture passages of the RdRp mutant strains are available in JGV Online.







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