id author title date pages extension mime words sentences flesch summary cache txt cord-301285-p83ondy8 Kautz, Tiffany F Low-fidelity Venezuelan equine encephalitis virus polymerase mutants to improve live-attenuated vaccine safety and efficacy 2018-03-06 .txt text/plain 8836 472 53 To validate the safety of low-fidelity mutations to increase vaccine attenuation, several mutations in the RNA-dependent RNA-polymerase (RdRp) were tested in the live-attenuated Venezuelan equine encephalitis virus vaccine strain, TC-83. Due to the error-prone nature of the RNA-dependent RNApolymerase (RdRp), RNA virus replication is characterized by a high mutation rate that results in increased genetic diversity of progeny viruses (Domingo et al. When compared with unpassaged, wild-type (wt) viruses, fidelity mutants have similar growth kinetics in vitro, but are attenuated in vivo due to the alteration of diversity produced during replication, which hampers the ability of the virus to overcome bottlenecks in the host (Pfeiffer and Kirkegaard 2005; Vignuzzi et al. The 4x mutant, while exhibiting phenotypic similarities with other altered fidelity mutants, had no significant difference in virus diversity compared with the TC-83 parent after one cell culture passage. ./cache/cord-301285-p83ondy8.txt ./txt/cord-301285-p83ondy8.txt