Impacts of different expressions of PA-X protein on 2009 pandemic H1N1 virus replication, pathogenicity and host immune responses

Virology. 2017 Apr:504:25-35. doi: 10.1016/j.virol.2017.01.015. Epub 2017 Jan 29.

Abstract

Although several studies have investigated the functions of influenza PA-X, the impact of different expressions of PA-X protein including full-length, truncated or PA-X deficient forms on virus replication, pathogenicity and host response remains unclear. Herein, we generated two mutated viruses expressing a full-length or deficient PA-X protein based on the A/California/04/2009 (H1N1) virus that expresses a truncated PA-X to understand three different expressions of PA-X protein on virus replication, pathogenicity and host immune responses. The results showed that expression of either full-length or truncated PA-X protein enhanced viral replication and pathogenicity as well as reduced host innate immune response in mice by host shutoff activity when compared to the virus expressing the deficient PA-X form. Furthermore, the full-length PA-X expression exhibited a greater effect on virus pathogenicity than the truncated PA-X form. Our results provide novel insights of PA-X on viral replication, pathogenicity and host immune responses.

Keywords: Host immune response; Influenza A virus; PA-X; Virus replication.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Cell Line
  • Cell Line, Tumor
  • Dogs
  • Female
  • Gene Expression Regulation, Viral / genetics*
  • HEK293 Cells
  • Humans
  • Inflammation / genetics
  • Inflammation / immunology
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza A Virus, H1N1 Subtype / pathogenicity*
  • Lung / immunology
  • Lung / pathology
  • Lung / virology
  • Madin Darby Canine Kidney Cells
  • Mice
  • Mice, Inbred BALB C
  • Mutation / genetics
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / pathology
  • Orthomyxoviridae Infections / virology*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Viral Nonstructural Proteins / genetics*
  • Viral Nonstructural Proteins / metabolism
  • Virus Replication / genetics

Substances

  • PA-X protein, influenza A virus
  • Protein Isoforms
  • Repressor Proteins
  • Viral Nonstructural Proteins