title: Computer-aided codon-pairs deoptimization of the major envelope GP5 gene attenuates porcine reproductive and respiratory syndrome virus.
abstract: 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.
authors: Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
authors: Yan-Yan
authors: YY
authors: Ni
authors: Department of Computer Science, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
authors: Zhao
authors: Z
authors: Zhao
authors: Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.
authors: Tanja
authors: T
authors: Opriessnig
authors: Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
authors: Sakthivel
authors: S
authors: Subramaniam
authors: 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.
authors: Lei
authors: L
authors: Zhou
authors: Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
authors: Dianjun
authors: D
authors: Cao
authors: Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
authors: Qian
authors: Q
authors: Cao
authors: College of Veterinary Medicine, China Agricultural University, Beijing, People's Republic of China.
authors: Hanchun
authors: H
authors: Yang
authors: Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA. Electronic address: xjmeng@vt.edu.
authors: Xiang-Jin
authors: XJ
authors: Meng
mesh_terms: D000818:Animals; D001483:Base Sequence; D003062:Codon; D017076:Computer-Aided Design; D005818:Genetic Engineering; D008969:Molecular Sequence Data; D019318:Porcine Reproductive and Respiratory Syndrome / Q000821:virology*; D019316:Porcine respiratory and reproductive syndrome virus / Q000235:genetics* / Q000502:physiology; D013552:Swine; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
chemical_list: D003062:Codon; D014759:Viral Envelope Proteins; C114789:glycoprotein 5, PRRSV
keywords: Attenuation; GP5 gene; Porcine reproductive and respiratory syndrome virus (PRRSV); Synthetic attenuated virus engineering (SAVE)