Identification of viral genes associated with the interferon-inducing phenotype of a synthetic porcine reproductive and respiratory syndrome virus strain

Virology. 2016 Dec:499:313-321. doi: 10.1016/j.virol.2016.09.018. Epub 2016 Oct 11.

Abstract

We recently generated a fully synthetic porcine reproductive and respiratory syndrome virus strain (designated as PRRSV-CON), which confers unprecedented levels of heterologous protection. We report herein that the synthetic PRRSV-CON possesses a unique phenotype in that it induces type-I interferons (IFNs) instead of suppressing these cytokines as most of the naturally occurring PRRSV isolates do. Through gain- and loss- of-function studies, the IFN-inducing phenotype of PRRSV-CON was mapped to the 3.3kb genomic fragment encoding three viral nonstructural proteins: nsp1α, nsp1β and the N-terminal part of nsp2. Further studies indicated that a cooperation among these 3 proteins was required for effective induction of IFNs. Collectively, this study constitutes the first step toward understanding the mechanisms by which the synthetic PRRSV-CON confers heterologous protection.

Keywords: Innate immunity; PRRSV; Reverse genetics; Synthetic virus.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Genes, Synthetic*
  • Genome, Viral
  • Interferon-beta / genetics*
  • Interferon-beta / metabolism
  • Phenotype
  • Porcine Reproductive and Respiratory Syndrome / genetics
  • Porcine Reproductive and Respiratory Syndrome / metabolism
  • Porcine Reproductive and Respiratory Syndrome / virology*
  • Porcine respiratory and reproductive syndrome virus / chemistry
  • Porcine respiratory and reproductive syndrome virus / genetics*
  • Porcine respiratory and reproductive syndrome virus / metabolism
  • Swine
  • Viral Nonstructural Proteins / chemical synthesis*
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism

Substances

  • Viral Nonstructural Proteins
  • Interferon-beta