Zurück zu Ihrem Suchergebnis

Beschreibung

Hepatitis C virus (HCV) is a small (~55-65 nm), enveloped, positive-sense single-stranded RNA virus that is a causative factor for hepatitis C and hepatocellular carcinoma. HCV expresses several proteins that promote viral replication. Genome polyprotein of HCV can be cleaved into 11 different chains. The mature core protein packages viral RNA to form a viral nucleocapsid, and promotes virion budding. It also prevents the establishment of cellular antiviral state by blocking the interferon- a/b and interferon- g signaling pathways and by inducing STAT1 degradation. Envelope proteins E1 and E2 form a heterodimer, which is involved in virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. Viroprotein P7, a heptameric ion channel protein, plays an essential role in the assembly, envelopment, and secretion of viral particles. HCV polyprotein also contains NS2, a cysteine protease and NS3, a serine protease. NS2 is required for the proteolytic auto-cleavage between NS2 and NS3. NS3 binds a single ATP and catalyzes the unzipping of a single base pair of dsRNA. It also inhibits host antiviral proteins TBK1 and IRF3 and prevents the establishment of an antiviral state. Non-structural protein 4A (NS4A), a peptide cofactor, forms a non-covalent complex with the N-terminal of NS3 and this complex prevents phosphorylation of host IRF3, which also prevents the establishment of dsRNA induced antiviral state. NS4B induces a specific membrane alteration that serves as a scaffold for the virus replication complex. Non-structural protein 5A (NS5A), a multi-functional phosphoprotein, is an RNA-binding peripheral membrane protein that is reported to antagonize numerous cellular pathways, including the antiviral interferon- a response. It can bind to the 3'-ends of HCV plus and minus strand RNAs. NS5A exists as hypo- and hyper-phosphorylated forms and the dynamic transition between these two states is involved in the functions of NS5A. Hyperphosphorylation occurs primarily at its six serine residues within the low complexity sequence of NS5A. Phosphorylated NS5A is shown to be essential for viral replication and assembly. (Ref.: Kandangwa, M. and Liu, Q. (2019). Biochem. Biophys. Res. Commmun. 520(1), 192-197, Saeed, M., et al. (2015). Nature. 524(7566), 471-475, Huang, L., et al. (2005). J. Biol. Chem. 280(43), 36417-36428).