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The non-pathogenic Henipavirus Cedar paramyxovirus phosphoprotein has a compromised ability to target STAT1 and STAT2

Kim G Lieu1, Glenn A Marsh2, Lin-Fa Wang3

  • 1Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria, Australia.

Antiviral Research
|November 4, 2015
PubMed

Insights

Lethal henipaviruses like Hendra virus evade the immune system by targeting STAT proteins. The non-pathogenic Cedar paramyxovirus shows a weaker ability to antagonize these proteins, suggesting a compromised interferon response.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Lethal henipaviruses, Hendra virus (HeV) and Nipah virus, employ P gene products (phosphoprotein P, V, and W) to antagonize the interferon (IFN) signaling pathway by targeting STAT1 and STAT2 proteins.
  • The immune evasion mechanisms of the non-pathogenic Henipavirus, Cedar paramyxovirus (CedPV), particularly its interaction with STAT proteins, remain largely uncharacterized.

Purpose of the Study:

  • To comparatively analyze the ability of Hendra virus (HeV) P gene products and Cedar paramyxovirus (CedPV) P protein to antagonize the IFN/STAT signaling pathway.
  • To investigate the differences in STAT protein interaction and subsequent inhibition of IFN-inducible gene expression between HeV and CedPV.

Main Methods:

  • Comparative analysis of HeV P gene products (P/V/W) and CedPV-P using immunoprecipitation assays.
  • Quantitative confocal microscopy to assess the interaction and relocalization of STAT1 and STAT2 proteins.
  • Measurement of mRNA synthesis for the IFN-inducible gene MxA.
  • Infection studies with HeV and CedPV to evaluate inhibition of IFN-α-mediated STAT1 nuclear accumulation.

Main Results:

  • Differences were observed in the ability of HeV P gene products and CedPV-P to engage STAT1 and STAT2 proteins.
  • CedPV-P exhibited compromised interaction with and relocalization of STAT1 or STAT2 compared to HeV proteins.
  • The reduced interaction of CedPV-P with STAT proteins correlated with a diminished capacity to inhibit MxA mRNA synthesis.
  • Hendra virus demonstrated greater potency than CedPV in inhibiting IFN-α-induced STAT1 nuclear accumulation.

Conclusions:

  • Cedar paramyxovirus P protein has a compromised ability to interact with and antagonize STAT1 and STAT2 proteins compared to Hendra virus P gene products.
  • The impaired IFN/STAT antagonism by CedPV suggests a reduced capacity for immune evasion relative to pathogenic henipaviruses.
  • These findings highlight variations in immune evasion strategies among henipaviruses, with implications for understanding viral pathogenesis.
Keywords:
Cedar virusHendra virusHenipavirusInnate immunityInterferonPathogenesisSignal transducers and activators of transcription

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