The immune evasion function of J and Beilong virus V proteins is distinct from that of other paramyxoviruses, consistent with their inclusion in the proposed genus Jeilongvirus

J Gen Virol. 2016 Mar;97(3):581-592. doi: 10.1099/jgv.0.000388. Epub 2015 Dec 24.

Abstract

IFN-antagonist function is a major determinant of pathogenicity and cross-species infection by viruses, but remains poorly defined for many potentially zoonotic viruses resident in animal species. The paramyxovirus family contains several zoonotic viruses, including highly pathogenic viruses such as Nipah virus and Hendra virus, and an increasing number of largely uncharacterized animal viruses. Here, we report the characterization of IFN antagonism by the rodent viruses J virus (JPV) and Beilong virus (BeiPV) of the proposed genus Jeilongvirus of the paramyxoviruses. Infection of cells by JPV and BeiPV was found to inhibit IFN-activated nuclear translocation of signal transducer and activator of transcription 1 (STAT1). However, in contrast to most other paramyxoviruses, the JPV and BeiPV V proteins did not interact with or inhibit signalling by STAT1 or STAT2, suggesting that JPV/BeiPV use an atypical V protein-independent strategy to target STATs, consistent with their inclusion in a separate genus. Nevertheless, the V proteins of both viruses interacted with melanoma differentiation-associated protein 5 (MDA5) and robustly inhibited MDA5-dependent activation of the IFN-β promoter. This supports a growing body of evidence that MDA5 is a universal target of paramyxovirus V proteins, such that the V-MDA5 interaction represents a potential target for broad-spectrum antiviral approaches.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / immunology
  • HEK293 Cells
  • Humans
  • Immune Evasion*
  • Interferon-Induced Helicase, IFIH1
  • Interferon-alpha / genetics
  • Interferon-alpha / immunology
  • Paramyxoviridae Infections / genetics
  • Paramyxoviridae Infections / immunology*
  • Paramyxoviridae Infections / virology
  • Paramyxovirinae / classification
  • Paramyxovirinae / genetics
  • Paramyxovirinae / immunology*
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / immunology
  • STAT2 Transcription Factor / genetics
  • STAT2 Transcription Factor / immunology
  • Signal Transduction
  • Viral Proteins / genetics
  • Viral Proteins / immunology*

Substances

  • Interferon-alpha
  • STAT1 Transcription Factor
  • STAT2 Transcription Factor
  • V protein, Paramyxovirus
  • Viral Proteins
  • IFIH1 protein, human
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1