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Attenuation of Foot-and-Mouth Disease Virus by Engineering Viral Polymerase Fidelity.

J Virol.. 2017-07; 
Rai DK,Diaz-San Segundo F,Campagnola G,Keith A,Schafer EA,Kloc A,de Los Santos T,Peersen O,Rieder E.
Products/Services Used Details Operation
Catalog Products ... 139 140 Recombinant FMDV 3Dpol carrying specific amino acid substitutions. A synthetic codon 141 optimized gene for FMDV-A24 WT polymerase was purchased from Genscript Inc. (Piscataway, 142 on May 19, 2017 by Google Indexer http://jvi.asm.org/ Downloaded from ... Get A Quote

摘要

Foot-and-mouth disease virus (FMDV) RNA-dependent RNA polymerase (RdRp) (3Dpol) catalyzes viral RNA synthesis. Its characteristic low fidelity and absence of proofreading activity allow FMDV to rapidly mutate and adapt to dynamic environments. In this study, we used the structure of FMDV 3Dpol in combination with previously reported results from similar picornaviral polymerases to design point mutations that would alter replication fidelity. In particular, we targeted Trp237 within conserved polymerase motif A because of the low reversion potential inherent in the single UGG codon. Using biochemical and genetic tools, we show that the replacement of tryptophan 237 with phenylalanine imparts higher fidelity, but... More

关键词

3D polymerase; 3Dpol; RNA-dependent RNA polymerase fidelity; foot-and-mouth disease virus; picornavirus