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Excerpt
Chronic hepatitis C is a serious public health problem and a disease burden in many parts of the world. The discovery of the causative agent, hepatitis C virus (HCV), in 1989 has initiated an almost unparalleled research activity in academic and pharmaceutical-industry laboratories over the ensuing years. This book aims to provide a state-of-the-art account of recent advances in the molecular and cellular biology, immunology and pathogenesis of HCV. It also aspires to discuss new strategies as well as outstanding issues for future research.
Hepatitis C has been dubbed the “silent epidemic” because it is generally asymptomatic for decades after infection; its victims often are unaware of the infection until it is too late for therapy. What is the genetic makeup and molecular features that make HCV such a “silent” yet deadly assassin? This question, in fact, is the premise by which this monograph was prepared – it was an attempt to decode the secrets of HCV, one viral gene at a time. To that end, we assembled a team of highly regarded experts from different disciplines who have prepared 16 chapters on various aspects of HCV, including the HCV genome and the role(s) of each viral gene product within the context of the viral life cycle, host interactions, and regulation of host antiviral defense and adaptive immunity.
Contents
- Contributors
- PrefaceSeng-Lai Tan, Ph.D.
- IntroductionDavid R. Gretch.
- 1. HCV Genome and Life CycleStéphane Chevaliez and Jean-Michel Pawlotsky.
- 2. HCV 5′ and 3′UTR: When Translation Meets ReplicationStephanie T Shi and Michael M C Lai.
- 3. Assemble and Interact: Pleiotropic Functions of the HCV Core ProteinStephen J Polyak, Kevin C Klein, Ikuo Shoji, Tatsuo Miyamura, and Jaisri R Lingappa.
- 4. HCV Glycoproteins: Assembly of a Functional E1–E2 HeterodimerMuriel Lavie, Anne Goffard, and Jean Dubuisson.
- 5. HCV NS2/3 ProteaseSarah Welbourn and Arnim Pause.
- 6. HCV NS3-4A Serine ProteaseChao Lin.
- 7. HCV Helicase: Structure, Function, and InhibitionDavid N Frick.
- 8. HCV NS4B: From Obscurity to Central StageElla H Sklan and Jeffrey S Glenn.
- Introduction
- Proteolytic Generation of NS4B
- Subcellular Localization and Topology
- NS4B and Lipid Rafts
- The Immunological Effects of NS4B
- Modulation of Ns5bs' RNA-Dependent RNA Polymerase Activity
- Effects of NS4B on Translation
- "Membranous Web" Formation
- Modulation of ER Functions
- Malignant Transformation
- NS4B Features That May Underlie the Mechanisms of the Above Functions
- Future Directions
- Future Directions
- References
- 9. HCV NS5A: A Multifunctional Regulator of Cellular Pathways and Virus ReplicationYupeng He, Kirk A Staschke, and Seng-Lai Tan.
- 10. Biochemical Activities of the HCV NS5B RNA-Dependent RNA PolymeraseC T Ranjith-Kumar and C Cheng Kao.
- Introduction
- Expression of NS5B
- Structural Features of HCV NS5B
- Catalytic Pocket
- Activities of NS5B
- De novo Synthesis and Primer Extension
- Mutational Analysis
- Terminal Nucleotidyl Transferase (TNTase) Activity
- Template Switch
- Interaction with Other HCV Nonstructural Proteins
- Conclusion and Future Trends
- References
- 11. HCV Replicon SystemsKeril J Blight and Elizabeth A Norgard.
- Introduction
- Development of HCV Replicons
- Identification of Adaptive Mutations
- Generation of Replicons from Other HCV Isolates
- Development of Alternative Replicon Derivatives
- Cell Lines Permissive for HCV Replication
- Applications of the HCV Replicon System
- Inhibition of Replicon Replication
- Concluding Remarks
- References
- 12. Animal Models for HCV StudyLinda B Couto and Alexander A Kolykhalov.
- 13. HCV Regulation of Host DefenseD Spencer Carney and Michael Gale Jr.
- Introduction
- Innate Intracellular Immune Defenses
- ISG Products Have Antiviral Functions
- Cross-Talk Between Innate and Adaptive Immune Defenses
- IFN-γ Activation of the Antiviral Response
- Hepatic Defenses Are Triggered by HCV
- Triggering the Host Response to HCV Infection
- Regulation and Evasion of the Host Response by HCV
- HCV Regulation of IFN Signaling
- Regulation of ISG Expression or Function
- Viral Genetics Impact the Host Response to HCV Infection
- Exogenous Induction of Antiviral Hepatic Defenses
- The HCV/Host Interface Model of Viral Evasion
- References
- 14. Regulation of Adaptive Immunity by HCVXiao-Song He.
- 15. Recombinant Vesicular Stomatitis Virus (VSV) and Other Strategies in HCV Vaccine Designs and ImmunotherapyAyaz M Majid and Glen N Barber.
- Introduction
- Classical Strategies in Viral Vaccines
- Studies of Recombinant HCV Protein Sub-Units in Chimpanzees
- Efficacy of Recombinant DNA Approaches in Generating HCV Immunity
- Hepatitis C Virus-like Particles
- VSV as a Safe and Potent Vector for Generating Immunity against Viral Pathogens
- VSV-HCV Pseudotypes as a Prelude to Recombinant VSV in HCV Immuno-Intervention
- Replication Competent and Defective Recombinant VSV as a Vaccine Strategy to Generate Immune Responses
- Recombinant VSV Vaccine Studies
- VSV Expressing HCV Core, E1 and E2 Structural Proteins as a Potential Vaccine and Immunotherapeutic Strategy against HCV Infection
- Conclusions
- Future Trends
- References
- 16. Development of an Infectious HCV Cell Culture SystemTakaji Wakita and Takanobu Kato.
- Introduction
- A Case of Fulminant Hepatitis Associated with HCV
- Sequence Analysis of JFH-1
- Preferential Processing for Core Protein of JFH-1
- Replication Capacity of JFH-1 as a Subgenomic Replicon
- Construction of Full-Length JFH-1 cDNA
- Replication of Full-Length JFH-1 RNA in Huh7 Cells
- Infectivity of Secreted Viral Particles from JFH-1 Transfected Cells
- Neutralization of JFH-1 Infectivity by CD81 Antibody and Patient Sera
- In Vivo Infectivity of JFH-1 Culture Medium
- Permissive Cells for JFH-1 Infection
- Summary and Concluding Remarks
- References
- NLM CatalogRelated NLM Catalog Entries
- Review Virology and cell biology of the hepatitis C virus life cycle: an update.[J Hepatol. 2014]Review Virology and cell biology of the hepatitis C virus life cycle: an update.Dubuisson J, Cosset FL. J Hepatol. 2014 Nov; 61(1 Suppl):S3-S13. Epub 2014 Nov 3.
- Review Mechanisms of hepatitis C virus infection.[Antivir Chem Chemother. 2003]Review Mechanisms of hepatitis C virus infection.Moriishi K, Matsuura Y. Antivir Chem Chemother. 2003 Nov; 14(6):285-97.
- Pathogen-Associated Molecular Pattern Recognition of Hepatitis C Virus Transmitted/Founder Variants by RIG-I Is Dependent on U-Core Length.[J Virol. 2015]Pathogen-Associated Molecular Pattern Recognition of Hepatitis C Virus Transmitted/Founder Variants by RIG-I Is Dependent on U-Core Length.Kell A, Stoddard M, Li H, Marcotrigiano J, Shaw GM, Gale M Jr. J Virol. 2015 Nov; 89(21):11056-68. Epub 2015 Aug 26.
- Review Hepatitis C virus (HCV): a review of immunological aspects.[Int Rev Immunol. 2008]Review Hepatitis C virus (HCV): a review of immunological aspects.Irshad M, Khushboo I, Singh S, Singh S. Int Rev Immunol. 2008; 27(6):497-517.
- Review Cellular and molecular biology of HCV infection and hepatitis.[Clin Sci (Lond). 2009]Review Cellular and molecular biology of HCV infection and hepatitis.Tang H, Grisé H. Clin Sci (Lond). 2009 Jun 15; 117(2):49-65. Epub 2009 Jun 15.
- Hepatitis C VirusesHepatitis C Viruses
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