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Helicase Domain of West Nile Virus NS3 Protein Plays a Role in Inhibition of Type I Interferon Signalling
- Source :
- Viruses; Volume 9; Issue 11; Pages: 326, Viruses, Viruses, Vol 9, Iss 11, p 326 (2017)
- Publication Year :
- 2017
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2017.
-
Abstract
- West Nile virus (WNV) is a neurotropic flavivirus that can cause encephalitis in mammalian and avian hosts. In America, the virulent WNV strain (NY99) is causing yearly outbreaks of encephalitis in humans and horses, while in Australia the less virulent Kunjin strain of WNV strain has not been associated with significant disease outbreaks until a recent 2011 large outbreak in horses (but not in humans) caused by NSW2011 strain. Using chimeric viruses between NY99 and NSW2011 strains we previously identified a role for the non-structural proteins of NY99 strain and especially the NS3 protein, in enhanced virus replication in type I interferon response-competent cells and increased virulence in mice. To further define the role of NY99 NS3 protein in inhibition of type I interferon response, we have generated and characterised additional chimeric viruses containing the protease or the helicase domains of NY99 NS3 on the background of the NSW2011 strain. The results identified the role for the helicase but not the protease domain of NS3 protein in the inhibition of type I interferon signalling and showed that helicase domain of the more virulent NY99 strain performs this function more efficiently than helicase domain of the less virulent NSW2011 strain. Further analysis with individual amino acid mutants identified two amino acid residues in the helicase domain primarily responsible for this difference. Using chimeric replicons, we also showed that the inhibition of type I interferon (IFN) signalling was independent of other known functions of NS3 in RNA replication and assembly of virus particles.
- Subjects :
- 0301 basic medicine
NS3
medicine.medical_treatment
viruses
030106 microbiology
lcsh:QR1-502
Virulence
Viral Nonstructural Proteins
Virus Replication
lcsh:Microbiology
Virus
Article
03 medical and health sciences
Mice
flavivirus
Interferon
Virology
medicine
Animals
Humans
Protease
biology
Virus Assembly
DNA Helicases
Helicase
virus diseases
interferon
biology.organism_classification
Flavivirus
helicase
030104 developmental biology
Infectious Diseases
Viral replication
Interferon Type I
biology.protein
West Nile virus
West Nile Fever
medicine.drug
Peptide Hydrolases
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 19994915
- Database :
- OpenAIRE
- Journal :
- Viruses; Volume 9; Issue 11; Pages: 326
- Accession number :
- edsair.doi.dedup.....c1984db194d8bf4529801f9de6d102f8
- Full Text :
- https://doi.org/10.3390/v9110326