Mutations in the highly conserved palm region of the plus-strand RNA virus RdRp result in viral attenuation in vitro, suggesting flexibility that could inform vaccine and viral vector development.
RdRp palm mutations attenuate plus-strand RNA viruses in vitro; hypothesis-generating for attenuated vaccines or vectors pending in vivo validation.
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.
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Gallei et al. (2006) studied this question.
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