id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-355357-b6aklh44	Stapleford, Kenneth A.	Viral Polymerase-Helicase Complexes Regulate Replication Fidelity To Overcome Intracellular Nucleotide Depletion	2015-08-26		.txt	text/plain	7650	342	43	IMPORTANCE Previous studies using the RNA mutagen ribavirin to select for drug-resistant variants have highlighted the essential role of the viral RNA-dependent RNA polymerase in regulating replication fidelity. Similar to other studies, we previously utilized the RNA mutagens ribavirin and 5-fluorouracil to study drug-resistant mutations in alphaviruses (CHIKV and SINV) and identified residue 483 of the RdRp nsP4 as a key determinant of polymerase fidelity (10, 11) . Furthermore, given that both the CHIKV high-fidelity polymerase variant nsP4 (C483Y) and the novel nsP2 (G641D) variants were isolated in the same antiviral treatment, we addressed their additive roles in resistance to the RNA mutagens ribavirin and 5-fluorouracil (Fig. 1B) . By treating cells during viral infection with each compound, we found that the high-fidelity nsP2 variant and double mutant were more resistant to both nucleotide-depleting compounds ( Fig. 7B and C) , similar to what we observed with ribavirin treatment.	./cache/cord-355357-b6aklh44.txt	./txt/cord-355357-b6aklh44.txt