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Helicase Domain of West Nile Virus NS3 Protein Plays a Role in Inhibition of Type I Interferon Signalling

Authors :
Nias Y. G. Peng
Parthiban Periasamy
Yin Xiang Setoh
Alexander A. Khromykh
Andrii Slonchak
Alberto A. Amarilla
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.

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