Nonstructural protein 3-4A: the Swiss army knife of hepatitis C virus
| Autor: | Morikawa, K., Lange, C. M., Gouttenoire, J., Meylan, E., Brass, V., Penin, F., Moradpour, D. |
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| Rok vydání: | 2011 |
| Předmět: |
Protein Tyrosine Phosphatase
Non-Receptor Type 2 Serine Proteinase Inhibitors viruses Intracellular Signaling Peptides and Proteins virus diseases Hepacivirus Hepatitis C Chronic Viral Nonstructural Proteins biochemical phenomena metabolism and nutrition Nucleoside-Triphosphatase Virus Replication Antiviral Agents digestive system diseases Mitochondrial Proteins Adaptor Proteins Vesicular Transport Drug Resistance Viral Mutation Humans Serine Proteases Carrier Proteins RNA Helicases Adaptor Proteins Signal Transducing Signal Transduction |
| Zdroj: | Journal of viral hepatitis |
| DOI: | 10.1111/j.1365-2893.2011.01451.x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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