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Nonstructural protein 3‐4A: the Swiss army knife of hepatitis C virus
Author(s) -
Morikawa K.,
Lange C. M.,
Gouttenoire J.,
Meylan E.,
Brass V.,
Penin F.,
Moradpour D.
Publication year - 2011
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/j.1365-2893.2011.01451.x
Subject(s) - ns3 , virology , ribavirin , protease , hepatitis c virus , ns2 3 protease , viral replication , serine protease , interferon , ns5a , innate immune system , biology , hepacivirus , virus , immune system , immunology , enzyme , biochemistry
Summary. Hepatitis C virus (HCV) nonstructural protein 3‐4A (NS3‐4A) is a complex composed of NS3 and its cofactor NS4A. It harbours serine protease as well as NTPase/RNA helicase activities and is essential for viral polyprotein processing, RNA replication and virion formation. Specific inhibitors of the NS3‐4A protease significantly improve sustained virological response rates in patients with chronic hepatitis C when combined with pegylated interferon‐α and ribavirin. The NS3‐4A protease can also target selected cellular proteins, thereby blocking innate immune pathways and modulating growth factor signalling. Hence, NS3‐4A is not only an essential component of the viral replication complex and prime target for antiviral intervention but also a key player in the persistence and pathogenesis of HCV. This review provides a concise update on the biochemical and structural aspects of NS3‐4A, its role in the pathogenesis of chronic hepatitis C and the clinical development of NS3‐4A protease inhibitors.