scholarly journals Building a mechanistic mathematical model of hepatitis C virus entry

2018 ◽  
Author(s):  
Mphatso Kalemera ◽  
Dilyana Mincheva ◽  
Joe Grove ◽  
Christopher J. R. Illingworth
Keyword(s):  
Mathematical Model ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Viral Entry ◽  
Productive Infection ◽  
Virus Particles ◽  
Quantitative Studies ◽  
Receptor Dynamics ◽  
Viral Lifecycle ◽  
The Impact

AbstractThe mechanism by which hepatitis C virus (HCV) gains entry into cells is a complex one, involving a broad range of host proteins. Entry is a critical phase of the viral lifecycle, and a potential target for therapeutic or vaccine-mediated intervention. However, the mechanics of HCV entry remain poorly understood. Here we describe a novel computational model of viral entry, encompassing the relationship between HCV and the key host receptors CD81 and SR-B1. We conduct experiments to thoroughly quantify the influence of an increase or decrease in receptor availability upon the extent of viral entry. We use these data to build and parameterise a mathematical model, which we then validate by further experiments. Our results are consistent with sequential HCV-receptor interactions, whereby initial interaction between the HCV E2 glycoprotein and SR-B1 facilitates the accumulation CD81 receptors, leading to viral entry. However, we also demonstrate that a small minority of virus can achieve entry in the absence of SR-B1. Our model estimates the impact of the different obstacles that viruses must surmount to achieve entry; among virus particles attaching to the cell surface, 20-35% accumulate sufficient CD81 receptors, of these 4-8% then complete the subsequent steps to achieve productive infection. Furthermore, we make estimates of receptor stoichiometry; between 3 and 6 CD81 receptors are likely to be required to achieve viral entry. Our model provides a tool to investigate the entry characteristics of HCV variants and outlines a framework for future quantitative studies of the multi-receptor dynamics of HCV entry.

Estimating the impact of hepatitis C virus therapy on future liver-related morbidity, mortality and costs related to chronic hepatitis C

2005 ◽  
Vol 42 (5) ◽  
pp. 639-645 ◽  
Author(s):  
María Buti ◽  
Ramón San Miguel ◽  
Max Brosa ◽  
Juan M. Cabasés ◽  
Montserrat Medina ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
The Impact

Differentiated cells in prolonged hypoxia produce highly infectious native‐like hepatitis C virus particles

Hepatology ◽  
2021 ◽  
Author(s):  
Jade Cochard ◽  
Anne Bull‐Maurer ◽  
Clovis Tauber ◽  
Julien Burlaud‐Gaillard ◽  
Frédéric Mazurier ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Particles ◽  
Differentiated Cells

The impact of inherited prothrombotic risk factors on individuals chronically infected with hepatitis C virus from a single source

2007 ◽  
Vol 14 (4) ◽  
pp. 255-259 ◽  
Author(s):  
C. Goulding ◽  
C. O'Brien ◽  
H. Egan ◽  
J. E. Hegarty ◽  
G. McDonald ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Single Source ◽  
Prothrombotic Risk Factors ◽  
The Impact

Floating density of hepatitis C virus particles and response to interferon treatment

1998 ◽  
Vol 55 (1) ◽  
pp. 12-17 ◽  
Author(s):  
Akito Sakai ◽  
Shuichi Kaneko ◽  
Eiki Matsushita ◽  
Kenichi Kobayashi
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Interferon Treatment ◽  
Virus Particles

scholarly journals The Impact of Human T-Cell Lymphotropic Virus I Infection on Clinical and Immunologic Outcomes in Patients Coinfected With HIV and Hepatitis C Virus

2011 ◽  
Vol 57 ◽  
pp. S202-S207 ◽  
Author(s):  
Fabianna Bahia ◽  
Vinicius Novais ◽  
Jennifer Evans ◽  
Chloe Le Marchand ◽  
Eduardo Netto ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Human T Cell ◽  
The Impact

The impact of direct-acting antivirals on liver fibrosis in Egyptian hepatitis C virus patients: a single center experience

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Nadia Abdelaaty Abdelkader ◽  
Amira Mahmoud AlBalakosy ◽  
Ahmed Fouad Helmy Sherief ◽  
Mohamed Soliman Gado
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Liver Fibrosis ◽  
Transient Elastography ◽  
Liver Stiffness ◽  
Treatment Unit ◽  
Non Invasive ◽  
One Year ◽  
The Impact

Abstract Background Hepatitis C virus (HCV) infection affects approximately 170 million people worldwide, causing liver cirrhosis and hepatocellular carcinoma (HCC) and leading to liver transplantation and ultimately death. Accurate evaluation of liver fibrosis in patients with chronic liver diseases is crucial, as liver fibrosis is important in order to make therapeutic decisions, determine prognosis of liver disease and to follow-up disease progression. Multiple non-invasive methods have been used successfully in the prediction of fibrosis; however, early changes in noninvasive biomarkers of hepatic fibrosis under effective antiviral therapy are widely unknown. The aim of this study is to evaluate changes of transient elastography values as well as FIB-4 and AST to platelet ratio index (APRI) in patients treated with DAAs. Objectives The aim beyond this study is to evaluate the changes in liver stiffness in hepatitis C Egyptian patients before and at least one year after treatment with DAAs using transient elastography and non-invasive liver fibrosis indices as FIB-4 and APRI scores. Patients and methods The present study was conducted on 100 patients with chronic hepatitis C patients attended to Ain Shams University Hospitals, Viral hepatitis treatment unit between October 2017 and December 2018, who were followed-up during treatment and after treatment for at least one year (retrospective and prospective study). Total number of cases during the study period was 117 patients. 17 patients were excluded from the study due to missed follow-up. Eventually, 100 patients were enrolled in the study fulfilling the inclusion criteria. Results The mean age of our patients is 47.9 years with Male predominance (52 males and 48 females). There was a significant improvement of, platelets counts, ALT and AST levels, which in turn cause significant improvement in FIB-4 and APRI scores. There was a significant improvement of liver stiffness after end of treatment, regardless of the DAA regimen used, as evidenced by Fibroscan. Conclusion Fibrosis regression –assessed by non-invasive markers of fibrosis is achievable upon removal of the causative agent.

scholarly journals Hepatitis C virus depends on E-cadherin as an entry factor and regulates its expression in epithelial-to-mesenchymal transition

2016 ◽  
Vol 113 (27) ◽  
pp. 7620-7625 ◽  
Author(s):  
Qisheng Li ◽  
Catherine Sodroski ◽  
Brianna Lowey ◽  
Cameron J. Schweitzer ◽  
Helen Cha ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cell Surface ◽  
Viral Entry ◽  
Epithelial To Mesenchymal Transition ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Entry Site ◽  
Mesenchymal Transition ◽  
E Cadherin

Hepatitis C virus (HCV) enters the host cell through interactions with a cascade of cellular factors. Although significant progress has been made in understanding HCV entry, the precise mechanisms by which HCV exploits the receptor complex and host machinery to enter the cell remain unclear. This intricate process of viral entry likely depends on additional yet-to-be-defined cellular molecules. Recently, by applying integrative functional genomics approaches, we identified and interrogated distinct sets of host dependencies in the complete HCV life cycle. Viral entry assays using HCV pseudoparticles (HCVpps) of various genotypes uncovered multiple previously unappreciated host factors, including E-cadherin, that mediate HCV entry. E-cadherin silencing significantly inhibited HCV infection in Huh7.5.1 cells, HepG2/miR122/CD81 cells, and primary human hepatocytes at a postbinding entry step. Knockdown of E-cadherin, however, had no effect on HCV RNA replication or internal ribosomal entry site (IRES)-mediated translation. In addition, an E-cadherin monoclonal antibody effectively blocked HCV entry and infection in hepatocytes. Mechanistic studies demonstrated that E-cadherin is closely associated with claudin-1 (CLDN1) and occludin (OCLN) on the cell membrane. Depletion of E-cadherin drastically diminished the cell-surface distribution of these two tight junction proteins in various hepatic cell lines, indicating that E-cadherin plays an important regulatory role in CLDN1/OCLN localization on the cell surface. Furthermore, loss of E-cadherin expression in hepatocytes is associated with HCV-induced epithelial-to-mesenchymal transition (EMT), providing an important link between HCV infection and liver cancer. Our data indicate that a dynamic interplay among E-cadherin, tight junctions, and EMT exists and mediates an important function in HCV entry.

Dynamical analysis of a class of hepatitis C virus infection models with application of optimal control

2016 ◽  
Vol 09 (03) ◽  
pp. 1650038 ◽  
Author(s):  
Aida Mojaver ◽  
Hossein Kheiri
Keyword(s):  
Optimal Control ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Deterministic Model ◽  
Treatment Strategies ◽  
Dynamical Analysis ◽  
Existence And Stability ◽  
Direct Cell ◽  
Infected Cells ◽  
The Impact

In this paper, we deal with the problem of optimal control of a deterministic model of hepatitis C virus (HCV). In the first part of our analysis, a mathematical modeling of HCV dynamics which can be controlled by antiretroviral therapy as fixed controls has been presented and analyzed which incorporates two mechanisms: infection by free virions and the direct cell-to-cell transmission. Basic reproduction number is calculated and the existence and stability of equilibria are investigated. In the second part, the optimal control problem representing drug treatment strategies of the model is explored considering control parameters as time-dependent in order to minimize not only the population of infected cells but also the associated costs. At the end of the paper, the impact of combination of the strategies in the control of HCV and their effectiveness are compared by numerical simulation.

scholarly journals Escape from HLA-B*08-Restricted CD8 T Cells by Hepatitis C Virus Is Associated with Fitness Costs

2008 ◽  
Vol 82 (23) ◽  
pp. 11803-11812 ◽  
Author(s):  
Shadi Salloum ◽  
Cesar Oniangue-Ndza ◽  
Christoph Neumann-Haefelin ◽  
Laura Hudson ◽  
Silvia Giugliano ◽  
...  
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Viral Replication ◽  
Consensus Sequence ◽  
Acute Infection ◽  
Spontaneous Clearance ◽  
Fitness Costs ◽  
Genotype 1B ◽  
The Impact

ABSTRACT The inherent sequence diversity of the hepatitis C virus (HCV) represents a major hurdle for the adaptive immune system to control viral replication. Mutational escape within targeted CD8 epitopes during acute HCV infection has been well documented and is one possible mechanism for T-cell failure. HLA-B*08 was recently identified as one HLA class I allele associated with spontaneous clearance of HCV replication. Selection of escape mutations in the immunodominant HLA-B*08-restricted epitope HSKKKCDEL1395-1403 was observed during acute infection. However, little is known about the impact of escape mutations in this epitope on viral replication capacity. Their previously reported reversion back toward the consensus residue in patients who do not possess the B*08 allele suggests that the consensus sequence in this epitope is advantageous for viral replication in the absence of immune pressure. The aim of this study was to determine the impact of mutational escape from this immunodominant epitope on viral replication. We analyzed it with a patient cohort with chronic HCV genotype 1b infection and in a single-source outbreak (genotype 1b). Sequence changes in this highly conserved region are rare and selected almost exclusively in the presence of the HLA-B*08 allele. When tested in the subgenomic replicon (Con1), the observed mutations reduce viral replication compared with the prototype sequence. The results provide direct evidence that escape mutations in this epitope are associated with fitness costs and that the antiviral effect of HLA-B*08-restricted T cells is sufficiently strong to force the virus to adopt a relatively unfavorable sequence.

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