Key result
Engineered mutations in the viral polymerase palm domain significantly altered in vitro nucleotide discrimination, strongly correlating with elongation rates and in vivo mutation frequencies.
Population
Viral RNA-dependent RNA polymerases (coxsackievirus B3 and poliovirus)
Comparison
Engineered mutations in the polymerase vs Wild-type or unmutated polymerases
Design
Preclinical
Authors
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Hypothesis-generating for palm-domain engineering in RNA virus attenuation; leaves open translation to safe human vaccines.
Single mutations in the polymerase palm domain of positive-strand RNA viruses can drastically alter mutation rates and attenuate virus growth, providing a potential pathway for developing live attenuated virus vaccines.
Campagnola et al. (2014) studied Viral infection (coxsackievirus B3, poliovirus). Engineered polymerase mutations vs. Wild-type polymerase was evaluated on In vitro nucleotide discrimination, elongation rates, and in vivo mutation frequencies. Engineered mutations in the viral polymerase palm domain significantly altered in vitro nucleotide discrimination, strongly correlating with elongation rates and in vivo mutation frequencies.
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