|
Hepatitis C
|
0.100 |
Biomarker
|
disease |
BEFREE |
Conclusion: Overall, our results indicate that NS5A contributes to the inhibition of innate immune pathways during HCV infection by exploiting the ability of LRPPRC to inhibit MAVS-regulated antiviral signaling.
|
30070380 |
2019 |
|
Hepatitis C
|
0.100 |
Biomarker
|
disease |
BEFREE |
Taken together, these data reveal that the NS4A Y16 residue regulates a noncanonical Riplet-TBK1-IRF3-dependent, but RIG-I-MAVS-independent, signaling pathway that limits HCV infection.<b>IMPORTANCE</b> The HCV NS3-NS4A protease complex facilitates viral replication by cleaving and inactivating the antiviral innate immune signaling proteins MAVS and Riplet, which are essential for RIG-I activation.
|
31534039 |
2019 |
|
Hepatitis C
|
0.100 |
Biomarker
|
disease |
BEFREE |
Detailed studies revealed that HCV infection activates MAVS that in turn recruits TRAF6 via TRAF-interacting-motifs (TIMs), and TRAF6 subsequently directly recruits GP73 to MAVS via coiled-coil domain.
|
28394926 |
2017 |
|
Hepatitis C
|
0.100 |
Biomarker
|
disease |
BEFREE |
The activity of asunaprevir-regulated innate immunity signal pathway was assessed with IFN-β promoter or IFN-stimulated responsive element (ISRE) reporter assays and immunoblotting of key signal proteins. siRNA-mediated MAVS and TRIF knockdown of cells was performed to assess the effect of asunaprevir-regulated innate immunity against HCV and DENV.
|
28473813 |
2017 |
|
Hepatitis C
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
The down regulation of TRIF, TLR3, and MAVS expressions in CHC correlates with the disease severity and the outcome of HCV infection.
|
28480979 |
2017 |
|
Hepatitis C
|
0.100 |
Biomarker
|
disease |
BEFREE |
Moreover, poly(rC) binding protein 2 (PCBP2) interacts with NLRX1 to participate in the NLRX1-induced degradation of MAVS and the inhibition of antiviral responses during HCV infection.
|
28956771 |
2017 |
|
Hepatitis C
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
We showed that HCV infection induced robust interferon response in the cells expressing MAVS resistant to the NS3-4A cleavage.
|
25463548 |
2015 |
|
Hepatitis C
|
0.100 |
Biomarker
|
disease |
BEFREE |
Using gene-disrupted mice and hydrodynamic injection strategy, we found the MAVS pathway to be crucial for induction of type III interferons (IFNs) in response to HCV in mouse.
|
26512676 |
2015 |
|
Hepatitis C
|
0.100 |
Biomarker
|
disease |
BEFREE |
First, using IPS-1 knockout mice, we revealed that IPS-1 was essential for type III IFN production by mouse hepatocytes and CD8(+) dendritic cells (DCs) in response to cytoplasmic HCV RNA.
|
24532585 |
2014 |
|
Hepatitis C
|
0.100 |
Biomarker
|
disease |
BEFREE |
HCV-encoded NS3/4A protease plays an important role in HCV immune evasion by cleaving key adapter proteins VISA and TRIF of the RIG-I-like receptors and Toll-like receptors mediated interferon (IFN) induction pathways.
|
23137809 |
2013 |
|
Hepatitis C
|
0.100 |
Biomarker
|
disease |
BEFREE |
The HCV NS3/4A protease efficiently cleaves and inactivates two important signaling molecules in the sensory pathways that react to HCV pathogen-associated molecular patterns (PAMPs) to induce interferons (IFNs), i.e., mitochondrial antiviral signaling protein (MAVS) and Toll-IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF).
|
23063572 |
2013 |
|
Hepatitis C
|
0.100 |
Biomarker
|
disease |
BEFREE |
In vitro studies suggested that type I and III IFNs are mainly produced in HCV-infected hepatocytes if the MAVS pathway is functional, and dysfunction of this pathway may lead to cellular permissiveness to HCV replication and production.
|
23292079 |
2013 |
|
Hepatitis C
|
0.100 |
Biomarker
|
disease |
BEFREE |
This resistance maps to single changes within the protease cleavage site in MAVS, which protect MAVS from getting cleaved by the HCV protease.
|
22427742 |
2012 |
|
Hepatitis C
|
0.100 |
Biomarker
|
disease |
BEFREE |
Here, we show that hydrophobic amino acids in the NS3 helix α(0) are required for selective cleavage of membrane-anchored portions of the HCV polyprotein and for cleavage of MAVS for control of RIG-I pathway signaling of innate immunity.
|
22238314 |
2012 |
|
Hepatitis C
|
0.100 |
Biomarker
|
disease |
BEFREE |
Although both IFNARko and IPS-1ko hepatocytes showed a reduced induction of type I interferons in response to viral infection, only IPS-1-/- cells circumvented cell death from HCV cytopathic effect and significantly improved J6JFH1 replication, suggesting IPS-1 to be a key player regulating HCV replication in mouse hepatocytes.
|
21731692 |
2011 |
|
Hepatitis C
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
A dominant active mutant of interferon (IFN) regulatory factor 7 (IRF7) and a negative regulator of HCV replication, VAP-C (Vesicle-associated membrane protein-associated protein subtype C), were fused with the C-terminal region of IPS-1 (IFNβ promoter stimulator-1), which includes an HCV protease cleavage site that was modified to be localized on the ER membrane, and designated cIRF7 and cVAP-C, respectively.
|
21253612 |
2011 |
|
Hepatitis C
|
0.100 |
Biomarker
|
disease |
BEFREE |
By specially cleaving VISA with hepatitis C virus (HCV) non-structural (NS)3/4A, the RIG-I pathway was blocked, with subsequent simultaneous inhibition of CD437-induced NF-kappaB activation and cell apoptosis in A375 cells.
|
18936944 |
2009 |
|
Hepatitis C
|
0.100 |
Biomarker
|
disease |
BEFREE |
CIFN exhibits increased anti-HCV potency over IFN-alpha2a and PEG-IFN through maximal and distinct induction of ISG expression and enhanced intracellular innate antiviral response, while protecting IPS-1 from HCV proteolysis.
|
19043919 |
2008 |
|
Hepatitis C
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Expression of the nonstructural protein (NS)3/4A protease in cells infected with hepatitis C virus (HCV) results in cleavage of the mitochondrial antiviral-signaling protein (MAVS) and disruption of signaling pathways that lead to viral activation of interferon regulatory factor 3 (IRF-3) and synthesis of type 1 interferons (IFN-alpha/beta).
|
18725224 |
2008 |
|
Hepatitis C
|
0.100 |
Biomarker
|
disease |
BEFREE |
HCV infection is supported by viral strategies to evade the innate antiviral response wherein the viral NS3.4A protease complex targets and cleaves the interferon promoter stimulator-1 (IPS-1) adaptor protein to ablate signaling of interferon alpha/beta immune defenses.
|
17289677 |
2007 |
|
Hepatitis C
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Co-expression of the NS3/4A protease activity of hepatitis C virus however blocked MAVS-mediated gene activation in a dose dependent manner.
|
16914100 |
2006 |
|
Hepatitis C
|
0.100 |
Biomarker
|
disease |
BEFREE |
Moreover, endogenous IPS-1 cleavage has not been demonstrated in the context of HCV infection in vitro or in vivo.
|
16585524 |
2006 |
|
Hepatitis C
|
0.100 |
Biomarker
|
disease |
LHGDN |
Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus.
|
16177806 |
2005 |