In:
PROTEOMICS, Wiley, Vol. 13, No. 23-24 ( 2013-12), p. 3442-3456
Kurzfassung:
Japanese encephalitis virus ( JEV ) nonstructural protein 5 ( NS 5) exhibits a T ype I interferon ( IFN ) antagonistic function. This study characterizes Type I IFN antagonism mechanism of NS 5 protein, using proteomic approach. In human neuroblastoma cells, NS 5 expression would suppress IFN β‐induced responses, for example, expression of IFN ‐stimulated genes PKR and OAS as well as STAT 1 nuclear translocation and phosphorylation. Proteomic analysis showed JEV NS 5 downregulating calreticulin, while upregulating cyclophilin A , HSP 60 and stress‐induced‐phosphoprotein 1. Gene silence of calreticulin raised intracellular C a 2+ levels while inhibiting nuclear translocalization of STAT 1 and NFAT ‐1 in response to IFN β, thus, indicating calreticulin downregulation linked with T ype I IFN antagonism of JEV NS 5 via activation of Ca 2+ /calicineurin. Calcineurin inhibitor cyclosporin A attenuated NS5‐mediated inhibition of IFN β‐induced responses, for example, IFN ‐sensitive response element driven luciferase, STAT 1‐dependent PKR m RNA expression, as well as phosphorylation and nuclear translocation of STAT 1. Transfection with calcineurin (vs. control) si RNA enhanced nuclear translocalization of STAT 1 and upregulated PKR expression in NS 5‐expressing cells in response to IFN β. Results prove C a 2+ , calreticulin, and calcineurin involvement in STAT 1‐mediated signaling as well as a key role of JEV NS 5 in T ype I IFN antagonism. This study offers insights into the molecular mechanism of T ype I interferon antagonism by JEV NS 5.
Materialart:
Online-Ressource
ISSN:
1615-9853
,
1615-9861
DOI:
10.1002/pmic.v13.23-24
DOI:
10.1002/pmic.201300001
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2013
ZDB Id:
2037674-1
SSG:
12
