Hepatitis C Virus Infection Is Inhibited by a Noncanonical Antiviral Signaling Pathway Targeted by NS3-NS4A
نویسندگان
چکیده
منابع مشابه
Modulation of hepatitis C virus NS5A hyperphosphorylation by nonstructural proteins NS3, NS4A, and NS4B.
NS5A of the hepatitis C virus (HCV) is a highly phosphorylated protein involved in resistance against interferon and required most likely for replication of the viral genome. Phosphorylation of this protein is mediated by a cellular kinase(s) generating multiple proteins with different electrophoretic mobilities. In the case of the genotype 1b isolate HCV-J, in addition to the basal phosphoryla...
متن کاملSelection of functional variants of the NS3-NS4A protease of hepatitis C virus by using chimeric sindbis viruses.
The NS3-NS4A serine protease of hepatitis C virus (HCV) mediates four specific cleavages of the viral polyprotein and its activity is considered essential for the biogenesis of the HCV replication machinery. Despite extensive biochemical and structural characterization, the analysis of natural variants of this enzyme has been limited by the lack of an efficient replication system for HCV in cul...
متن کاملDifferential requirements of NS4A for internal NS3 cleavage and polyprotein processing of hepatitis C virus.
The NS3 protein of hepatitis C virus (HCV) possesses protease activity responsible for the proteolytic cleavage of the viral polyprotein at the junctions of nonstructural proteins downstream of NS3. The NS3 protein was also found to be internally cleaved. In this study, we demonstrated that internal cleavages occurred on the NS3 protein of genotype 1b in the presence of NS4A, both in culture ce...
متن کاملThe N-terminal region of hepatitis C virus nonstructural protein 3 (NS3) is essential for stable complex formation with NS4A.
Hepatitis C virus proteins are produced by proteolytic processing of the viral precursor polyprotein that is encoded in the largest open reading frame of the viral genome. Processing of the nonstructural viral polyprotein requires the viral serine-type proteinase present in nonstructural protein 3 (NS3). The cleavage of the junction between NS4B and NS5A is mediated by NS3 only when NS4A is pre...
متن کاملHepatitis C virus NS2 is a protease stimulated by cofactor domains in NS3.
Chronic infection with hepatitis C virus (HCV) affects 130 million people worldwide and is a major cause of liver cirrhosis and liver cancer. After translation of the HCV RNA genome into a polyprotein, 2 viral proteases process its non-structural protein (NS) region. While the essential chymotrypsin-like serine protease NS3-4A mediates all cleavages downstream of NS3, the NS2-3 cysteine proteas...
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ژورنال
عنوان ژورنال: Journal of Virology
سال: 2019
ISSN: 0022-538X,1098-5514
DOI: 10.1128/jvi.00725-19