Key result
PA subunit R638A mutation severely attenuates influenza viral growth by promoting defective interfering RNAs.
Why the study?
The molecular mechanisms by which mutations in the PA subunit of influenza A virus RNA polymerase affect viral growth and defective interfering RNA synthesis were unclear.
The R638A mutation in the influenza PA subunit attenuates viral growth by destabilizing PA-RNA template interactions, providing insights into viral RNA polymerase function.
Hypothesis-generating for PA-targeted influenza attenuation; leaves open therapeutic translation pending in vivo validation.
An R638A mutation of the polymerase acidic protein (PA) subunit of the RNA polymerase of influenza A/WSN/33 virus results in severe attenuation of viral growth in cell culture by promoting the synthesis of defective interfering RNAs. We propose that R638A is an "elongation" mutant that destabilizes PA-RNA template interactions during elongation. A C453R mutation in PA can compensate for this defect, suggesting that amino acids C453 and R638 form part of the same domain.
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Fodor et al. (2003) studied Influenza A virus infection. R638A mutation of the polymerase acidic protein (PA) subunit was evaluated on Viral growth in cell culture and synthesis of defective interfering RNAs. An R638A mutation in the PA subunit of influenza A/WSN/33 virus RNA polymerase severely attenuated viral growth in cell culture by promoting defective interfering RNAs.
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