3.4.21.98: hepacivirin
This is an abbreviated version!
For detailed information about hepacivirin, go to the full flat file.
Reaction
Hydrolysis of four peptide bonds in the viral precursor polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr in P1 and Ser or Ala in P1'
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Synonyms
Cpro-2, Cpro-2 proteinase, Den2 protease, HCV NS3, HCV NS3 protease, HCV NS3/4A, HCV NS3/4A protease, Hepacivirin, hepatitis C virus NS3 serine protease, hepatitis C virus NS3/4A protease, non-structural 3 protein, nonstructural 3 protease, nonstructural protein 3, nonstructural protein 3-4A serine protease, nonstructural protein 3-4Agene, nonstructural protein 3/4A protease, NS2/3 protease, NS2B-NS3 proteinase, NS2B/NS3 protease, NS3, NS3 protease, NS3 protein, NS3 proteinase, NS3 serine protease, NS3 serine proteinase, NS3-4A, NS3-4A protease, NS3-4A serine protease, NS3-4A serine protease complex, NS3-4A serine proteinase, NS3-NS4A protease, NS3-protease, NS3-SP, NS3/4a, NS3/4A protease, NS3/4A protease complex, NS3/4A serine protease, NS34Agene, NS3?4A, NS5A-5B protease, P70, polyprotein-processing proteinase NS3, proteinase NS3, proteinase, polyprotein-processing, NS3, sc-protease, serine protease NS3, serine proteinase NS3
ECTree
General Information
General Information on EC 3.4.21.98 - hepacivirin
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evolution
Hepatitis C virus genotype 4a
NS3/4A protease from HCV genotype 4a is the most prevalent genotype in Egypt
evolution
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phylogenetic analyses of NS3 proteases sequences
evolution
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the hepatitis C virus (HCV) is a plus stranded RNA virus belonging to the Flaviviridae family. Despite the high mutation rate of HCV, the functionally important residues are highly conserved. These include residues that form the catalytic triad (His57, Asp81, and Ser139), the S1 and S6 pocket, zinc-binding site (Cys97, Cys99, Cys145, and His149) and the substrate binding groove. The epitopes B1, B8 and B9 are over 95% conserved across six major HCV genotypes
malfunction
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protease competent NS3 has a significant fibrogenic impact in expressing LX-2 cells when compared to protease defective NS3 or GFP control plasmids
malfunction
Hepatitis C virus genotype 2a
treatment of virus-infected cells with NS3 enzyme inhibitor BILN-2061 significantly increases degranulation against K-562 target cells and IFN-gamma productivity in natural killer (NK) cells of the host. The expression levels of activating NK cell receptors, such as NKp46 and NKp30, are also increased
physiological function
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the impact of NS3/4A protease activity and quasispecies complexity on virus clearance after IFN-based therapy is examined in HCV-HIV-1-coinfected patients: NS3/4A protease efficiency in cleaving caspase recruitment domain adaptor-inducing IFN-beta (Cardif) may be associated with the pegIFN-RBV treatment response
physiological function
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canine hepacivirus protease can disrupt the human innate antiviral defense signaling pathway suggesting a possible evolutionary relationship between canine hepacivirus and hepatitis C virus
physiological function
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generation of NS3/4A/Lap/LC-1 triple transgenic mouse liver-specifically and conditionally expressing reporter luciferase Fluc, Cre recombinase and reverse tetracycline-controlled transcriptional activator. NS3/4A protein is strictly and conditionally expressed in the liver of doxycycline-induced triple transgenic mice
physiological function
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intrahepatic expression of viral protease NS3/4A makes mice resistant to TNF-alpha-induced liver damage and causes an alteration of the intrahepatic cytokine IFN-g and IL-10 and chemokine CCL3, CCL17, CCL22, CXCL9, and CXCL11 profiles toward an anti-inflammatory state. The number of intrahepatic Th1 cells and IFN-g+ T cells in NS3/4A transgenic mice decreases, whereas the amount of Th2 cells increases. The NS3/4A-mediated effects are reversed by ribavirin treatment
physiological function
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membrane-associated peroxidase GPx8 is a cellular substrate of the hepatitis C virus NS3-4A protease. GPx8 is involved in viral particle production but not in HCV entry or RNA replication
physiological function
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viral NS3/4A protease activity is responsible for inhibition of hepatitis C virus genomic RNA-induced interferon IL-28 expression upon infection. Hepatitis C virus can trigger type III interferon expression in hosts. As a counter measurement, the virus blocks this antiviral response by using its own NS3/4A protease to target the key adaptor molecules that mediate the activation of NK-kappaB and IRF3
physiological function
Hepatitis C virus genotype 2a
hepatitis C virus impairs natural killer cell activity via viral serine protease NS3. The modulation of natural killer (NK) cell functions by HCV leads to an impaired innate immune response. In HCV-infected Huh-7.5 cells, the serine protease NS3 may play a role in the abrogation of NK cell functions in the early phase of infection through downregulation of NKp46 and NKp30 receptors on NK cells. HCV-NS replicon and HCV-NS3-transfected Huh-7.5 cells attenuate NK cell functions, overview
physiological function
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possible role of NS3 protease activity of hepatitis C virus in fibrogenesis and miR-122 expression in hepatic stellate cells. Various roles of hepatitis C virus (HCV) NS3 protein in viral pathogenesis are emphasized, especially in the progression of fibrosis and tumors. The expression of miR-122 is downregulated in LX-2 cells transfected with NS3 plasmids, encoding active or defective NS3s, irrespective of protease function. The protease function of NS3 protein is a crucial factor for the induction of hepatic fibrosis but it does not play a complete role in the expression of miR-122. The proteolytically active NS3 protein upregulates TGF-beta1 production
physiological function
Hepatitis C virus genotype 1b
the hepatitis C virus (HCV) NS3/4A protease that plays an important role in the viral life cycle
additional information
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baseline NS3 quasispecies diversity and complexity is higher in acutely infected subjects compared to a chronic hepatitis C control group. Both parameters are comparable in patients with spontaneous clearance versus treatment-induced acute hepatitis C or development of chronic hepatitis C. Longitudinal NS3 quasispecies kinetics show a trend to a decreasing diversity and complexity within 4 weeks in patients with spontaneous clearance compared to the other groups. Spontaneous clearance of acute hepatitis C, baseline clinical parameters of 82 patients with an acute hepatitis C and HIV coinfection, overview
additional information
Hepatitis C virus genotype 1b
HCV is a member of the Flaviviridae family consisting of a positive single strand RNA that encodes a polyprotein. This polyprotein is cleaved to the structural and nonstructural (NS) proteins by both host and viral proteases.4 The NS3 region is a trypsin-like serine protease that plays an essential role in viral replication and involves in processes to attenuate and evade the host cell's natural immune defense
additional information
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the location of possible B- and T-cell epitopes are predicted in the HCV NS3-4A consensus sequence