id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-002651-9r384oxd	Pauly, Matthew D.	Epistatic Interactions within the Influenza A Virus Polymerase Complex Mediate Mutagen Resistance and Replication Fidelity	2017-08-16		.txt	text/plain	8111	429	50	Studies of mutagen-resistant viruses have identified determinants of replicative fidelity and the importance of mutation rate to viral population dynamics. Consistent with the importance of epistatic interactions in the influenza virus polymerase, our data suggest that nucleoside analog resistance and replication fidelity are strain dependent. To this end, we identified variants within the polymerase complex of influenza virus that are able to tolerate drug-mediated increases in viral mutation rates. In most cases, mutagen-resistant variants encode polymerases that exhibit increased replication fidelity, and characterization of these mutants has elucidated the molecular mechanisms governing mutation rate. We tested each of the variant polymerases for reduced nucleoside sensitivity by comparing titers after replication of the corresponding virus populations in mock-or drug-treated cell cultures 24 h postinfection (Fig. 1A) . We used a serial passage competition assay (15) to measure the replicative fitness of each mutant virus relative to the WT PR8 and also performed growth curves to quantify RNA genome production.	./cache/cord-002651-9r384oxd.txt	./txt/cord-002651-9r384oxd.txt