Further investigations of HCV NS5A-interacting proteins containing CMA-targeting motifs may help to elucidate HCV-induced pathogenesis. HCV NS5A plays a crucial role in HCV-induced CMA. HCV NS5A promotes recruitment of HSC70 to the substrate protein HNF-1α. Hepatitis C virus (HCV) NS5A protein interacts with hepatocyte-nuclear factor 1α (HNF-1α) together with HSC70 and promotes the lysosomal degradation of HNF-1α via CMA, resulting in HCV-induced pathogenesis. CMA directly delivers a substrate protein into the lysosome lumen using the cytosolic chaperone HSC70 and the lysosomal receptor LAMP-2A for degradation. All proteins internalized in the lysosome via CMA contain a pentapeptide KFERQ-motif, also known as a CMA-targeting motif, which is necessary for selectivity. Although autophagy is considered a nonselective degradation process, CMA is known as a selective degradation pathway. There are three types of autophagy macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). Lysosome incorporate and degrade proteins in a process known as autophagy. 2Department of Clinical Microbiology, Faculty of Medicine, Udayana University, Bali, Indonesia.1Division of Infectious Disease Control, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan.Chieko Matsui 1†, Putu Yuliandari 1,2†, Lin Deng 1, Takayuki Abe 1 and Ikuo Shoji 1*
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