The NS5A protein of the hepatitis C virus genotype 1a is cleaved by caspases to produce C-terminal-truncated forms of the protein that reside mainly in the cytosol.

The Journal of Biological Chemistry
M KalamvokiP Mavromara

Abstract

The nonstructural 5A (NS5A) protein of the hepatitis C virus (HCV) is a multifunctional protein that is implicated in viral replication and pathogenesis. We report here that NS5A of HCV-1a is cleaved at multiple sites by caspase proteases in transfected cells. Two cleavage sites at positions Asp154 and 248DXXD251 were mapped. Cleavage at Asp154 has been previously recognized as one of the caspase cleavage sites for the NS5A protein of HCV genotype 1b (1, 2) and results in the production of a 17-kDa fragment. The sequence 248DXXD251 is a novel caspase recognition motif for NS5A and is responsible for the production of a 31-kDa fragment. Furthermore, we show that Arg217 is implicated in the production of the previously described 24-kDa product, whose accumulation is affected by both calpain and caspase inhibitors. We also showed that caspase-mediated cleavage occurs in the absence of exogenous proapoptotic stimuli and is not related to the accumulation of the protein in the endoplasmic reticulum. Interestingly, our data indicate that NS5A is targeted by at least two different caspases and suggest that caspase 6 is implicated in the production of the 17-kDa fragment. Most importantly, we report that, all the detectable NS5A fragme...Continue Reading

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Citations

May 20, 2008·Molecular & Cellular Proteomics : MCP·Guy KlaimanAndréa C Leblanc
Aug 30, 2008·Annual Review of Microbiology·Sonja M Best
Jan 14, 2012·Virology Journal·Lilian Ht YamasakiPaula Rahal
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May 13, 2014·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Eirini KaramichaliPenelope Mavromara
Aug 2, 2016·The International Journal of Biochemistry & Cell Biology·Ioanna VallianouMargarita Hadzopoulou-Cladaras
Oct 22, 2016·Archives of Virology·Jinxin XieChangchun Tu
Jan 14, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Qing LinShao Bo Su
Sep 18, 2008·The Journal of General Virology·Søren U NielsenGeoffrey L Toms

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