PMID- 24503075 OWN - NLM STAT- MEDLINE DCOM- 20140502 LR - 20140207 IS - 1096-0341 (Electronic) IS - 0042-6822 (Linking) VI - 450-451 DP - 2014 Feb TI - Computer-aided codon-pairs deoptimization of the major envelope GP5 gene attenuates porcine reproductive and respiratory syndrome virus. PG - 132-9 LID - S0042-6822(13)00672-7 [pii] LID - 10.1016/j.virol.2013.12.009 [doi] AB - Synthetic attenuated virus engineering (SAVE) is an emerging technology that enables rapid attenuation of viruses. In this study, by using SAVE we demonstrated rapid attenuation of an arterivirus, porcine reproductive and respiratory syndrome virus (PRRSV). The major envelope GP5 gene of PRRSV was codon-pair deoptimized aided by a computer algorithm. The codon-pair deoptimized virus, designated as SAVE5 with a deoptimized GP5 gene, was successfully rescued in vitro. The SAVE5 virus replicated at a lower level in vitro with a significant decrease of GP5 protein expression compared to the wild-type PRRSV VR2385 virus. Pigs experimentally infected with the SAVE5 virus had significantly lower viremia level up to 14 days post-infection as well as significantly reduced gross and histological lung lesions when compared to wild-type PRRSV VR2385 virus-infected pigs, indicating the attenuation of the SAVE5 virus. This study proved the feasibility of rapidly attenuating PRRSV by SAVE. CI - Copyright (c) 2013 Elsevier Inc. All rights reserved. FAU - Ni, Yan-Yan AU - Ni YY AD - Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA. FAU - Zhao, Zhao AU - Zhao Z AD - Department of Computer Science, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA. FAU - Opriessnig, Tanja AU - Opriessnig T AD - Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA. FAU - Subramaniam, Sakthivel AU - Subramaniam S AD - Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA. FAU - Zhou, Lei AU - Zhou L AD - Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA; College of Veterinary Medicine, China Agricultural University, Beijing, People's Republic of China. FAU - Cao, Dianjun AU - Cao D AD - Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA. FAU - Cao, Qian AU - Cao Q AD - Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA. FAU - Yang, Hanchun AU - Yang H AD - College of Veterinary Medicine, China Agricultural University, Beijing, People's Republic of China. FAU - Meng, Xiang-Jin AU - Meng XJ AD - Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA. Electronic address: xjmeng@vt.edu. LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20131231 PL - United States TA - Virology JT - Virology JID - 0110674 RN - 0 (Codon) RN - 0 (Viral Envelope Proteins) RN - 0 (glycoprotein 5, PRRSV) SB - IM MH - Animals MH - Base Sequence MH - *Codon MH - Computer-Aided Design MH - *Genetic Engineering MH - Molecular Sequence Data MH - Porcine Reproductive and Respiratory Syndrome/*virology MH - Porcine respiratory and reproductive syndrome virus/*genetics/physiology MH - Swine MH - Viral Envelope Proteins/*genetics/metabolism MH - Virus Replication OTO - NOTNLM OT - Attenuation OT - GP5 gene OT - Porcine reproductive and respiratory syndrome virus (PRRSV) OT - Synthetic attenuated virus engineering (SAVE) EDAT- 2014/02/08 06:00 MHDA- 2014/05/03 06:00 CRDT- 2014/02/08 06:00 PHST- 2013/08/17 00:00 [received] PHST- 2013/09/11 00:00 [revised] PHST- 2013/12/10 00:00 [accepted] PHST- 2014/02/08 06:00 [entrez] PHST- 2014/02/08 06:00 [pubmed] PHST- 2014/05/03 06:00 [medline] AID - S0042-6822(13)00672-7 [pii] AID - 10.1016/j.virol.2013.12.009 [doi] PST - ppublish SO - Virology. 2014 Feb;450-451:132-9. doi: 10.1016/j.virol.2013.12.009. Epub 2013 Dec 31.