Methionine-101 from one strain of H5N1 NS1 protein determines its IFN-antagonizing ability and subcellular distribution patternReportar como inadecuado




Methionine-101 from one strain of H5N1 NS1 protein determines its IFN-antagonizing ability and subcellular distribution pattern - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Science China Life Sciences

, Volume 55, Issue11, pp 933939

First Online: 03 November 2012Received: 19 August 2012Accepted: 20 September 2012DOI: 10.1007-s11427-012-4393-9

Cite this article as: Meng, J., Zhang, Z., Zheng, Z.
et al.
Sci.
China Life Sci.
2012 55: 933.
doi:10.1007-s11427-012-4393-9

Abstract

Influenza A virus NS1 protein has developed two main IFN-antagonizing mechanisms by inhibiting retinoic-acid-inducible gene I RIG-I signal transduction, or by suppressing cellular pre-mRNA processing through binding to cleavage and polyadenylation specific factor 30 CPSF30.
However, the precise effects of NS1 on suppressing type I IFN induction have not been well characterized.
Here we report that compared with PR-8-34 NS1, which is localized partially in the cytoplasm and has strong IFN-antagonizing ability via specifically inhibiting IFN- promoter activity, H5N1 NS1 has strikingly different characteristics.
It mainly accumulates in the nucleus of transfected cells and exerts rather weak IFN-counteracting ability through suppression of the overall gene expression.
The M101I mutation of H5N1 NS1, namely H5-M101I, fully reversed its functions.
H5-M101I gained the ability to specifically inhibit IFN- promoter activity, translocate to the cytoplasm, and release CPSF30.
The previously reported NES nuclear export signal residues 138147 was unable to lead H5N1 NS1 to translocate.
This suggests that other residues may serve as a potent NES.
Findings indicated that together with leucine-100, methionine-101 enhanced the regional NES.
In addition, methionine-101 was the key residue for the NS1-CPSF30 interaction.
This study reveals the importance of methionine-101 in the influenza A virus life cycle and may provide valuable information for antiviral strategies.

Keywordsinfluenza A virusH5N1NS1IFN-CPSF30NESThis article is published with open access at Springerlink.com

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Autor: JinMeng - ZhenFengZhang - ZhenHuaZheng - YanLiu - HanZhongWang

Fuente: https://link.springer.com/



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