PA from an H5N1 highly pathogenic avian influenza virus activates viral transcription and replication and induces apoptosis and interferon expression at an early stage of infection

Virol J. 2012 Jun 8;9:106. doi: 10.1186/1743-422X-9-106.

Abstract

Background: Although gene exchange is not likely to occur freely, reassortment between the H5N1 highly pathogenic avian influenza virus (HPAIV) and currently circulating human viruses is a serious concern. The PA polymerase subunit of H5N1 HPAIV was recently reported to activate the influenza replicon activity.

Methods: The replicon activities of PR8 and WSN strains (H1N1) of influenza containing PA from HPAIV A/Cambodia/P0322095/2005 (H5N1) and the activity of the chimeric RNA polymerase were analyzed. A reassortant WSN virus containing the H5N1 Cambodia PA (C-PA) was then reconstituted and its growth in cells and pathogenicity in mice examined. The interferon promoter, TUNEL, and caspase 3, 8, and 9 activities of C-PA-infected cells were compared with those of WSN-infected cells.

Results: The activity of the chimeric RNA polymerase was slightly higher than that of WSN, and C-PA replicated better than WSN in cells. However, the multi-step growth of C-PA and its pathogenicity in mice were lower than those of WSN. The interferon promoter, TUNEL, and caspase 3, 8, and 9 activities were strongly induced in early infection in C-PA-infected cells but not in WSN-infected cells.

Conclusions: Apoptosis and interferon were strongly induced early in C-PA infection, which protected the uninfected cells from expansion of viral infection. In this case, these classical host-virus interactions contributed to the attenuation of this strongly replicating virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Line
  • Female
  • Humans
  • Influenza A Virus, H1N1 Subtype / enzymology
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H1N1 Subtype / pathogenicity
  • Influenza A Virus, H1N1 Subtype / physiology
  • Influenza A Virus, H5N1 Subtype / enzymology*
  • Influenza A Virus, H5N1 Subtype / immunology
  • Influenza A Virus, H5N1 Subtype / pathogenicity
  • Influenza A Virus, H5N1 Subtype / physiology*
  • Interferons / biosynthesis*
  • Mice
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / pathology
  • Orthomyxoviridae Infections / virology
  • RNA-Dependent RNA Polymerase
  • Reassortant Viruses / enzymology
  • Reassortant Viruses / immunology
  • Reassortant Viruses / pathogenicity
  • Reassortant Viruses / physiology
  • Survival Analysis
  • Transcription, Genetic*
  • Viral Load
  • Viral Proteins
  • Virus Replication*

Substances

  • PA protein, influenza viruses
  • Viral Proteins
  • Interferons
  • RNA-Dependent RNA Polymerase