PMID- 26487085 OWN - NLM STAT- MEDLINE DCOM- 20160531 LR - 20201209 IS - 1465-2099 (Electronic) IS - 0022-1317 (Linking) VI - 97 IP - 1 DP - 2016 Jan TI - Amino acid residues Ala283 and His421 in the RNA-dependent RNA polymerase of porcine reproductive and respiratory syndrome virus play important roles in viral ribavirin sensitivity and quasispecies diversity. PG - 53-59 LID - 10.1099/jgv.0.000316 [doi] AB - The quasispecies diversity of RNA viruses is mainly determined by the fidelity of RNA-dependent RNA polymerase (RdRp) during viral RNA replication. Certain amino acid residues play an important role in determining the fidelity, and such residues can be substituted with other amino acids to produce virus strains with higher fidelity. In this study, two amino acid substitutions (A283T and H421Y) in the RdRp of porcine reproductive and respiratory syndrome virus (PRRSV) were identified under the selection of ribavirin. Preliminary data showed that two substitutions were involved in conferring PRRSV with the properties of increased ribavirin resistance and restricted quasispecies diversity. The results indicated that these two amino acid residues (Ala283 and His421) play a crucial role in PRRSV replication by affecting the fidelity of its RdRp. The results have important implications for understanding the molecular mechanism of PRRSV evolution and pathogenicity, and developing a safer modified live-attenuated vaccine (MLV) against PRRSV. FAU - Tian, Debin AU - Tian D AD - Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, USA. FAU - Meng, Xiang-Jin AU - Meng XJ AD - Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151019 PL - England TA - J Gen Virol JT - The Journal of general virology JID - 0077340 RN - 0 (Amino Acids) RN - 0 (Antiviral Agents) RN - 49717AWG6K (Ribavirin) RN - EC 2.7.7.48 (RNA-Dependent RNA Polymerase) SB - IM MH - Amino Acids/*genetics MH - Antiviral Agents/*pharmacology MH - *Drug Resistance, Viral MH - *Genetic Variation MH - Mutation, Missense MH - Porcine respiratory and reproductive syndrome virus/classification/*enzymology/genetics MH - RNA-Dependent RNA Polymerase/*genetics MH - Ribavirin/*pharmacology MH - Selection, Genetic EDAT- 2015/10/22 06:00 MHDA- 2016/06/01 06:00 CRDT- 2015/10/22 06:00 PHST- 2015/10/22 06:00 [entrez] PHST- 2015/10/22 06:00 [pubmed] PHST- 2016/06/01 06:00 [medline] AID - 10.1099/jgv.0.000316 [doi] PST - ppublish SO - J Gen Virol. 2016 Jan;97(1):53-59. doi: 10.1099/jgv.0.000316. Epub 2015 Oct 19.