- 作者: Yi-Hen Kou; Shang-Min Chou; Yi-Ming Wang; Ya-Tzu Chang; Shao-Yong Huang; Mei-Ying Jung; Yu-Hsu Huang; Mei-Ru Chen; Ming-Fu Chang; Shin C. Chang
- 作者服務機構: 1 Institute of Microbiology, National Taiwan University College of Medicine, No.1, Sec.1, Jen-Ai Road, Taipei, Taiwan, Republic of China; ; 2 Institute of Biochemistry and Molecular Biology, National Taiwan University College of Medicine, No.1, Sec.1, Jen-Ai Road, Taipei, Taiwan, Republic of China
- 中文摘要: --
- 英文摘要: The genomic RNA of hepatitis C virus (HCV) encodes the viral polyprotein precursor that undergoes proteolytic cleavage into structural and nonstructural proteins by cellular and the viral NS3 and NS2-3 proteases. Nonstructural protein 4A (NS4A) is a cofactor of the NS3 serine protease and has been demonstrated to inhibit protein synthesis. In this study, GST pull-down assay was performed to examine potential cellular factors that interact with the NS4A protein and are involved in the pathogenesis of HCV. A trypsin digestion followed by LC-MS/MS analysis revealed that one of the GST-NS4A-interacting proteins to be eukaryotic elongation factor 1A (eEF1A). Both the N-terminal domain of NS4A from amino acid residues 1-20, and the central domain from residues 21-34 interacted with eEFIA, but the central domain was the key player involved in the NS4A-mediated translation inhibition. NS4A(21-34) diminished both cap-dependent and HCV IRES-mediated translation in a dose-dependent manner. The translation inhibitory effect of NS4A(21-34) was relieved by the addition of purified recombinant eEF1A in an in vitro translation system. Taken together, NS4A inhibits host and viral translation through interacting with eEFIA, implying a possible mechanism by which NS4A is involved in the pathogenesis and chronic infection of HCV.
- 中文關鍵字: --
- 英文關鍵字: eEF1A, HCV, NS4A, translation inhibition, virus-host cell interactions