Reactome: A Curated Pathway Database
THIS SITE IS USED FOR CURATION AND TESTING
IT IS NOT STABLE, IS LINKED TO AN INCOMPLETE DATA SET, AND IS NOT MONITORED FOR PERFORMANCE. WE STRONGLY RECOMMEND THE USE OF OUR PUBLIC SITE

Query author contributions in Reactome

Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.

If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.

Name Email address

Details on Person Hepatitis C virus (HCV) is a member of the Hepacivirus genus...

Class:IdSummation:9731821
_displayNameHepatitis C virus (HCV) is a member of the Hepacivirus genus...
_timestamp2021-05-27 01:33:34
created[InstanceEdit:9731811] Shamovsky, Veronica, 2021-05-25
literatureReference[LiteratureReference:9731842] Hepatitis C virus NS3/4A protease
[LiteratureReference:9731782] Methods to Visualize MAVS Subcellular Localization
[LiteratureReference:9731840] Mitochondrial-associated endoplasmic reticulum membranes (MAM) form innate immune synapses and are targeted by hepatitis C virus
[LiteratureReference:9731835] New details of HCV NS3/4A proteinase functionality revealed by a high-throughput cleavage assay
[LiteratureReference:9731806] Nonstructural protein 3-4A: the Swiss army knife of hepatitis C virus
[LiteratureReference:9731825] Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus
[LiteratureReference:9731827] Control of innate immune signaling and membrane targeting by the Hepatitis C virus NS3/4A protease are governed by the NS3 helix α0
[LiteratureReference:9731818] Hepacivirus NS3/4A Proteases Interfere with MAVS Signaling in both Their Cognate Animal Hosts and Humans: Implications for Zoonotic Transmission
[LiteratureReference:9731845] Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity
[LiteratureReference:9731781] Structural determinants for membrane association and dynamic organization of the hepatitis C virus NS3-4A complex
[LiteratureReference:9731795] Subcellular localization, stability, and trans-cleavage competence of the hepatitis C virus NS3-NS4A complex expressed in tetracycline-regulated cell lines
[LiteratureReference:9731803] Recruitment of an interferon molecular signaling complex to the mitochondrial membrane: disruption by hepatitis C virus NS3-4A protease
[LiteratureReference:9731850] Dissociation of a MAVS/IPS-1/VISA/Cardif-IKKepsilon molecular complex from the mitochondrial outer membrane by hepatitis C virus NS3-4A proteolytic cleavage
[LiteratureReference:9731844] MAVS dimer is a crucial signaling component of innate immunity and the target of hepatitis C virus NS3/4A protease
[LiteratureReference:9732213] Structural biology of hepatitis C virus
modified[InstanceEdit:9732211] Shamovsky, Veronica, 2021-05-27
textHepatitis C virus (HCV) is a member of the Hepacivirus genus. HCV nonstructural protein 3 (ns3) forms a complex with a cofactor ns4A (Kwong AD et al. 1999; Shiryaev SA et al. 2012). The viral ns3 harbors serine protease activity at the N-terminal and a nucleoside-triphosphatase- (NTPase-) dependent RNA helicase activity (NTPase/RNA helicase) at the C-terminal (Penin F et al. 2004). Both enzyme activities are essential for viral replication. In addition, ns3:ns4A was found to modulate host antiviral responses (reviewed in Morikawa K et al. 2011). The mitochondrial antiviral signaling (MAVS) protein is one of the targets of ns3:ns4A (Li XD et al. 2005; Meylan E et al. 2005; Hiscott J et al. 2006; Horner SM et al. 2012). MAVS acts downstream of the cytosolic RNA sensors DDX58 and IFIH1 to coordinate activation of the transcription factors such as NF-kappaB and IFN regulatory factor 3 (IRF3) thus leading to induction of type-I, III interferons. The viral ns3:ns4A cleaves MAVS at Cys-508, causing the N-terminal fragment of MAVS to dislocate from the mitochondria resulting in inactive MAVS, which blocks DDX58/IFIH1 signaling pathway (Li XD et al. 2005; Lin R et al. 2006). The HCV ns3:ns4A-mediated cleavage of MAVS also disrupted oligomerization of MAVS, which is crusial for the MAVS adaptor activity (Baril M et al. 2009). Further, subcellular localization studies mapped ns3 and ns4A to the endoplasmic reticulum (ER) or an ER-like modified compartment (Wölk B et al. 2000). Mature MAVS resides at intracellular membranes, namely the mitochondria, peroxisomes, and the mitochondrial-associated ER membrane (MAM) (Vazquez C et al. 2017). At the MAM region, ER and mitochondria are tightly associated. The localization of MAVS to MAM suggests that the ER resident ns3:ns4A interacts with MAVS at MAM (Horner SM et al. 2011). Structural and biochemical analyses demonstrated that ns3:ns4A associates with intracellular membranes through membrane-targeting domains within ns4A and also at the amphipathic helix α(0) of ns3 (Brass V et al. 2008; Horner SM et al. 2012). In addition, ns3:ns4A proteases from nonhuman viruses of the genus Hepacivirus readily cleaved human MAVS, suggesting that the cleavage of MAVS is a common strategy of hepaciviruses (Anggakusuma et al. 2016).

This Reactome event shows the cleavage of MAVS at Cys-508 mediated by the HCV ns3:ns4A complex.

(summation)[BlackBoxEvent:9731775] HCV ns3:ns4A cleaves MAVS [Homo sapiens]
[Change default viewing format]
No pathways have been reviewed or authored by Hepatitis C virus (HCV) is a member of the Hepacivirus genus... (9731821)
Follow Reactome