scholarly journals Hepatitis C virus entry: molecular mechanisms and targets for antiviral therapy

10.2741/3450 ◽  
2009 ◽  
Vol Volume (14) ◽  
pp. 3274 ◽  
Author(s):  
Mirjam, B. Zeisel
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Therapy ◽  
Molecular Mechanisms ◽  
Virus Entry

scholarly journals Hepatitis C Virus Entry: An Intriguingly Complex and Highly Regulated Process

2020 ◽  
Vol 21 (6) ◽  
pp. 2091 ◽  
Author(s):  
Che Colpitts ◽  
Pei-Ling Tsai ◽  
Mirjam Zeisel
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Viral Entry ◽  
Chronic Infection ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Virus Entry ◽  
Host Factors ◽  
Entry Inhibitors

Hepatitis C virus (HCV) is a major cause of chronic hepatitis and liver disease worldwide. Its tissue and species tropism are largely defined by the viral entry process that is required for subsequent productive viral infection and establishment of chronic infection. This review provides an overview of the viral and host factors involved in HCV entry into hepatocytes, summarizes our understanding of the molecular mechanisms governing this process and highlights the therapeutic potential of host-targeting entry inhibitors.

scholarly journals An Entropic Safety Catch Controls Hepatitis C Virus Entry and Antibody Resistance

2020 ◽  
Author(s):  
Lenka Stejskal ◽  
Mphatso D. Kalemera ◽  
Machaela Palor ◽  
Lucas Walker ◽  
Tina Daviter ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Molecular Mechanisms ◽  
Virus Entry ◽  
Hypervariable Region ◽  
Intrinsically Disordered Protein ◽  
Conformational Entropy ◽  
Neutralising Antibodies ◽  
Intrinsically Disordered ◽  
Antibody Resistance

E1 and E2 (E1E2), the entry proteins of Hepatitis C Virus (HCV), are unlike that of any other virus yet described, and the detailed molecular mechanisms of HCV entry/fusion remain unknown. Hypervariable region-1 (HVR-1) of E2 is a putative intrinsically disordered protein tail. Here, we demonstrate that HVR-1 has an autoinhibitory function that suppresses the activity of E1E2 on free virions; this is dependent on its conformational entropy. Crucially, to allow entry, this mechanism is turned off by host receptor interactions at the cell surface. Thus, HVR-1 is akin to a safety catch on E1E2 activity. Mutations that reduce conformational entropy in HVR-1, or genetic deletion of HVR-1, turn off the safety catch to generate hyper-reactive HCV that exhibits enhanced virus entry but is thermally unstable and acutely sensitive to neutralising antibodies. Therefore, the HVR-1 safety catch controls the efficiency of virus entry and maintains resistance to neutralising antibodies.

scholarly journals Hepatitis C virus entry into hepatocytes: Molecular mechanisms and targets for antiviral therapies

2011 ◽  
Vol 54 (3) ◽  
pp. 566-576 ◽  
Author(s):  
Mirjam B. Zeisel ◽  
Isabel Fofana ◽  
Samira Fafi-Kremer ◽  
Thomas F. Baumert
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Molecular Mechanisms ◽  
Virus Entry ◽  
Antiviral Therapies

scholarly journals EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy

2011 ◽  
Vol 17 (5) ◽  
pp. 589-595 ◽  
Author(s):  
Joachim Lupberger ◽  
Mirjam B Zeisel ◽  
Fei Xiao ◽  
Christine Thumann ◽  
Isabel Fofana ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Therapy ◽  
Virus Entry ◽  
Host Factors

Effects of Smoking on Pegylated Interferon alpha 2a and First Generation Protease Inhibitor-based Antiviral Therapy in Naïve Patients Infected with Hepatitis C Virus Genotype 1

2016 ◽  
Vol 25 (1) ◽  
pp. 15-24 ◽  
Author(s):  
Tim Zimmermann ◽  
Dietrich Hueppe ◽  
Stefan Mauss ◽  
Peter Buggisch ◽  
Heike Pfeiffer-Vornkahl ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Therapy ◽  
Interferon Alpha ◽  
Virological Response ◽  
Sustained Viral Response ◽  
Pegylated Interferon ◽  
Genotype 1 ◽  
Pegylated Interferon Alpha ◽  
Viral Response

Background & Aims: Smoking has multiple effects on factors influencing hepatitis C and antiviral therapy, including lipid metabolism, fibrosis, platelet count and adherence aspects. The aim of this analysis was to determine the impact of smoking on hepatitis C virus antiviral therapy. Methods: Data of two cohorts of an observational multicenter study including therapy-naïve patients infected with genotype 1 hepatitis C virus (HCV) treated with dual antiviral therapy (n=7,796) with pegylated interferon alpha 2a in combination with ribavirin, or triple antiviral therapy (n=1,122) containing telaprevir or boceprevir, were analysed. Results: In the univariate matched pair analysis of dual antiviral therapy patients (n=584), smoking was significantly associated with lower sustained viral response rates (p=0.026, OR 0.69 CI: 0.50 – 0.96). The effect of smoking on sustained viral response remained significant (p=0.028, OR 0.67 CI: 0.47 – 0.96) in the multivariate analysis when adjusting for all other baseline parameters with a significant association in the univariate analysis, i.e. diabetes, fibrosis, body mass index, transaminases and baseline viral load. Under protease inhibitors the influence of smoking on virological response did not arise. Conclusions: Smoking has a negative impact on antiviral therapy in naïve patients infected with HCV genotype 1 independently of age, gender, history of drug use or alcoholic liver disease. The effects of smoking might be overcome by the new antiviral agents.Abbreviations: APRI: AST to platelet ratio index; DAA: direct antiviral agent; DT: dual antiviral therapy; EoTR: end of treatment response; RVR: rapid virological response; EVR: early virological response; HCV: hepatitis C virus; IFN: interferon alpha; MPA: Matched Pair Analysis; NS: non-smokers; PEG-IFN: pegylated interferon alpha 2a; PI: protease inhibitor; RBV: ribavirin; SAE: serious adverse event; SOC: standard of care; S: smokers; SVR: sustained viral response.    

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