Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Proteomics 2013 ; 13 (23-24): 3442-56 Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Proteomic analysis for Type I interferon antagonism of Japanese encephalitis virus NS5 protein #MMPMID24166946
Yang T; Li S; Lai C; Lu K; Chiu M; Hsieh T; Wan L; Lin C
Proteomics 2013[Dec]; 13 (23-24): 3442-56 PMID24166946show ga
Japanese encephalitis virus (JEV) nonstructural protein 5 (NS5) exhibits a Type I interferon (IFN) antagonistic function. This study characterizes Type I IFN antagonism mechanism of NS5 protein, using proteomic approach. In human neuroblastoma cells, NS5 expression would suppress IFN??induced responses, for example, expression of IFN?stimulated genes PKR and OAS as well as STAT1 nuclear translocation and phosphorylation. Proteomic analysis showed JEV NS5 downregulating calreticulin, while upregulating cyclophilin A, HSP 60 and stress?induced?phosphoprotein 1. Gene silence of calreticulin raised intracellular Ca2+ levels while inhibiting nuclear translocalization of STAT1 and NFAT?1 in response to IFN?, thus, indicating calreticulin downregulation linked with Type I IFN antagonism of JEV NS5 via activation of Ca2+/calicineurin. Calcineurin inhibitor cyclosporin A attenuated NS5?mediated inhibition of IFN??induced responses, for example, IFN?sensitive response element driven luciferase, STAT1?dependent PKR mRNA expression, as well as phosphorylation and nuclear translocation of STAT1. Transfection with calcineurin (vs. control) siRNA enhanced nuclear translocalization of STAT1 and upregulated PKR expression in NS5?expressing cells in response to IFN?. Results prove Ca2+, calreticulin, and calcineurin involvement in STAT1?mediated signaling as well as a key role of JEV NS5 in Type I IFN antagonism. This study offers insights into the molecular mechanism of Type I interferon antagonism by JEV NS5.