Truncation of C-terminal 20 amino acids in PA-X contributes to adaptation of swine influenza virus in pigs

Sci Rep. 2016 Feb 25:6:21845. doi: 10.1038/srep21845.

Abstract

The PA-X protein is a fusion protein incorporating the N-terminal 191 amino acids of the PA protein with a short C-terminal sequence encoded by an overlapping ORF (X-ORF) in segment 3 that is accessed by + 1 ribosomal frameshifting, and this X-ORF exists in either full length or a truncated form (either 61-or 41-condons). Genetic evolution analysis indicates that all swine influenza viruses (SIVs) possessed full-length PA-X prior to 1985, but since then SIVs with truncated PA-X have gradually increased and become dominant, implying that truncation of this protein may contribute to the adaptation of influenza virus in pigs. To verify this hypothesis, we constructed PA-X extended viruses in the background of a "triple-reassortment" H1N2 SIV with truncated PA-X, and evaluated their biological characteristics in vitro and in vivo. Compared with full-length PA-X, SIV with truncated PA-X had increased viral replication in porcine cells and swine respiratory tissues, along with enhanced pathogenicity, replication and transmissibility in pigs. Furthermore, we found that truncation of PA-X improved the inhibition of IFN-I mRNA expression. Hereby, our results imply that truncation of PA-X may contribute to the adaptation of SIV in pigs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism
  • Animals
  • Cell Line
  • Dogs
  • Genes, Reporter
  • Influenza A Virus, H1N2 Subtype / growth & development
  • Influenza A Virus, H1N2 Subtype / metabolism
  • Influenza A Virus, H1N2 Subtype / pathogenicity*
  • Interferon Type I / metabolism
  • Lung / pathology
  • Lung / virology
  • Madin Darby Canine Kidney Cells
  • Microscopy, Fluorescence
  • Nasal Cavity / virology
  • Orthomyxoviridae Infections / pathology*
  • Orthomyxoviridae Infections / virology
  • Real-Time Polymerase Chain Reaction
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Swine
  • Swine Diseases / pathology*
  • Swine Diseases / virology
  • Trachea / virology
  • Viral Nonstructural Proteins / chemistry
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism*

Substances

  • Amino Acids
  • Interferon Type I
  • PA-X protein, influenza A virus
  • Recombinant Proteins
  • Repressor Proteins
  • Viral Nonstructural Proteins