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Virology. 2014 Feb;450-451:132-9. doi: 10.1016/j.virol.2013.12.009. Epub 2013 Dec 31.

Computer-aided codon-pairs deoptimization of the major envelope GP5 gene attenuates porcine reproductive and respiratory syndrome virus.

Author information

  • 1Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
  • 2Department of Computer Science, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
  • 3Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.
  • 4Department 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.
  • 5College of Veterinary Medicine, China Agricultural University, Beijing, People's Republic of China.
  • 6Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA. Electronic address: xjmeng@vt.edu.

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.

Copyright © 2013 Elsevier Inc. All rights reserved.

KEYWORDS:

Attenuation; GP5 gene; Porcine reproductive and respiratory syndrome virus (PRRSV); Synthetic attenuated virus engineering (SAVE)

PMID:
24503075
[PubMed - indexed for MEDLINE]
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