Molecular Mechanisms of Hepatitis C Virus Entry – Impact of Host Cell Factors for Initiation of Viral Infection

2015 ◽  
pp. 189-202
Author(s):  
Mirjam Zeisel ◽  
Thomas Baumert
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Viral Infection ◽  
Host Cell ◽  
Molecular Mechanisms ◽  
Virus Entry ◽  
Host Cell Factors

The influence of cholesterol and lipid metabolism on host cell structure and hepatitis C virus replication

2006 ◽  
Vol 84 (1) ◽  
pp. 67-79 ◽  
Author(s):  
Selena M Sagan ◽  
Yanouchka Rouleau ◽  
Cynthia Leggiadro ◽  
Lubica Supekova ◽  
Peter G Schultz ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Lipid Metabolism ◽  
Hepatitis C ◽  
Host Cell ◽  
Molecular Mechanisms ◽  
Cholesterol Metabolism ◽  
Cell Structure ◽  
Metabolic Inhibitors ◽  
General Effect ◽  
Cellular Lipid

The hepatitis C virus (HCV) replicates on a membrane protein complex composed of viral proteins, replicating RNA, and altered cellular membranes. Small-molecule inhibitors of cellular lipid–cholesterol metabolism such as 25-hydroxycholesterol, cerulenin, lovastatin, and GGTI-286 all show a negative effect on HCV replication. Perturbation of host cell lipid and cholesterol metabolism can disrupt replication complexes by altering membranous structures where replication occurs. Changes in cholesterol and (or) lipid composition can have a general effect on membrane structure. Alternatively, metabolic changes can exert a more subtle influence over replication complexes by altering localization of host proteins through alterations in lipid anchoring. Here, we use Huh-7 cells harboring subgenomic HCV replicons to demonstrate that 25-hydroxycholesterol, cerulenin, lovastatin, and GGTI-286 do not disrupt the membranous web where replication occurs, whereas cholesterol-depleting agents such as β-cyclodextrin do. Cellular imaging suggests that the HCV RNA can remain associated with subcellular compartments connected with replication complexes in the presence of metabolic inhibitors. Therefore, at least 2 different molecular mechanisms are possible for the inhibition of HCV replication through the modulation of cellular lipid and cholesterol metabolism.Key words: hepatitis C virus, lipid metabolism, fluorescence microscopy, electron microscopy, membranous web, statins.

scholarly journals Molecular Mechanisms of Viral and Host Cell Substrate Recognition by Hepatitis C Virus NS3/4A Protease

2011 ◽  
Vol 85 (13) ◽  
pp. 6106-6116 ◽  
Author(s):  
K. P. Romano ◽  
J. M. Laine ◽  
L. M. Deveau ◽  
H. Cao ◽  
F. Massi ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Host Cell ◽  
Molecular Mechanisms ◽  
Substrate Recognition ◽  
Cell Substrate

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.

Identification of host cell factors involved in hepatitis C virus replication

2019 ◽  
Author(s):  
K Tabata ◽  
D Paul ◽  
B Brügger ◽  
G Superti-Furga ◽  
R Bartenschlager
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Host Cell ◽  
Virus Replication ◽  
Host Cell Factors

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 Affinity Capture and Identification of Host Cell Factors Associated with Hepatitis C Virus (+) Strand Subgenomic RNA

2013 ◽  
Vol 12 (6) ◽  
pp. 1539-1552 ◽  
Author(s):  
Alok Upadhyay ◽  
Updesh Dixit ◽  
Dinesh Manvar ◽  
Nootan Chaturvedi ◽  
Virendra N. Pandey
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Host Cell ◽  
Affinity Capture ◽  
Subgenomic Rna ◽  
Factors Associated ◽  
Host Cell Factors
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