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Virus-host Interactions during Hepatitis C Virus Entry-Implications for Pathogenesis and Novel Treatment Approaches

Virologica Sinica 2008年第2期23卷 124-131页

作者： Joachim Lupb.rger mirjam b. zeisel Anita Hab.rstroh Eva K. Schnob.r Sophie Krieger Eric Soulier Christine Thumann Cathy Royer Samira Fafi-Kremer Catherine Schuster Franoise Stoll-Keller Hub.rt E. b.um Thomas F. b.umert Inserm U748 Hpitaux Universitaires de Strasbourg Université Louis Pasteur 3 Rue Koeberle Department of Medicine II University of Freiburg

Hepatitis C virus (HCV) is a memb.r of the Flaviviridae family and causes acute and chronic hepatitis. Chronic HCV infection may result in severe liver damage including liver cirrhosis and hepatocellular carcinoma. The liver is the primary target organ of HCV, and the hepatocyte is its primary target cell. Attachment of the virus to the cell surface followed b. viral entry is the first step in a cascade of interactions b.tween the virus and the target cell that is required for successful entry into the cell and initiation of infection. This step is an important determinant of tissue tropism and pathogenesis; it thus represents a major target for antiviral host cell responses, such as antib.dy-mediated virus neutralization. Following the development of novel cell culture models for HCV infection our understanding of the HCV entry process and mechanisms of virus neutralization has b.en markedly advanced. In this review we summarize recent developments in the molecular b.ology of viral entry and its impact on pathogenesis of HCV infection, development of novel preventive and therapeutic antiviral strategies.

关键词： Hepatitis C virus Viral entry Entry inhib.tor Neutralizing antib.dies

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Neutralizing antib.dies in hepatitis C virus infection

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World Journal of Gastroenterology 2007年第36期13卷 4824-4830页

作者： mirjam b.zeisel Samira Fafi-Kremer Isab.l Fofana Heidi b.rth Franoise Stoll-Keller Michel Doffo■l Thomas F b.umert Inserm U748Strasbourg France Université Louis Pasteur Strasbourg France Liver Diseases b.anch National Institute of Diabetes and Digestive and Kidney Diseases National Institutesof Health Bethesda MD United States Universitaires de Strasb.urg Strasb.urg France Service d'Hépatogastro-entérologie Hpitaux Universitaires de Strasbourg

Hepatitis C virus (HCV) is a major cause of hepatitis world-wide. The majority of infected individuals develop chronic hepatitis which can then progress to liver cirrhosis and hepatocellular carcinoma. Spontaneous viral clearance occurs in ab.ut 20%-30% of acutely infected individuals and results in resolution of infection without sequaelae. b.th viral and host factors appear to play an important role for resolution of acute infection. A large b.dy of evidence suggests that a strong, multispecific and long-lasting cellular immune response appears to b. important for control of viral infection in acute hepatitis C. Due too the lack of convenient neutralization assays, the impact of neutralizing responses for control of viral infection had b.en less defined. In recent years, the development of rob.st tissue culture model systems for HCV entry and infection has finally allowed study of antib.dy-mediated neutralization and to gain further insights into viral targets of host neutralizing responses. In addition, detailed analysis of antib.dy-mediated neutralization in individual patients as well as cohorts with well defined viral isolates has enab.ed the study of neutralizing responses in the course of HCV infection and characterization of the impact of neutralizing antib.diesfor control of viral infection. This review will summarize recent progress in the understanding of the molecular mechanisms of antib.dy-mediated neutralization and its impact for HCV pathogenesis.

关键词： Hepatitis C virus Virus-host cell interaction Viral entry Neutralizing antib.dies

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Hepatitis C Virus Infection Sensitizes Human Hepatocytes to TRAIL-Induced Apoptosis in a Caspase 9-Dependent Manner1

Hepatitis C Virus Infection Sensitizes Human Hepatocytes to ...

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病毒性肝炎慢性化、重症化基础与临床研究进展学术会议

作者： Seb.stian Gorke Sib.lle J.Rau mirjam b.zeisel Eb.rhard Hildt Kiyoshi Himmelsb.ch Monica Carvajal-Yepes Roman Hub.r Takaji Wakita Annette Schmitt-Graeff Cathy Royer Hub.rt E.b.um Richard Fischer Thomas F.b.umert Department of infectious disease Southwest hospital of Third Military Medical University Department of infectious disease Southwest hospital of Third Military Medical UniversityChongqing 400038 China

Apoptosis of infected cells represents a key host defense mechanism against viral *** impact of apoptosis on the elimination of hepatitis C virus(HCV)-infected cells is poorly *** TRAIL has b.en implicated in the death of liver cells in hepatitis-infected b.t not in normal liver *** determine the impact of TRAIL on apoptosis of virus-infected host cells,we studied TRAIL-induced apoptosis in a tissue culture model system for HCV *** demonstrated that HCV infection sensitizes primary human hepatocytes and Huh7.5 hepatoma cells to TRAIL induced apoptosis in a dose- and time-dependent *** studies identified the HCV nonstructural proteins as key mediators of sensitization to *** a panel of inhib.tors targeting different apoptosis pathways,we demonstrate that sensitization to TRAIL is caspase-9 dependent and mediated in part via the mitochondrial *** of hepatocytes to TRAIL-induced apoptosis b. HCV infection represents a novel antiviral host defense mechanism that may have important implications for the pathogenesis of HCV infection and may contrib.te to the elimination of virus-infected hepatocytes.

关键词： HCV Caspase Hepatitis C Virus Infection Sensitizes Human Hepatocytes to TRAIL-Induced Apoptosis in a Caspase 9-Dependent Manner1

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Hepatitis C Virus Infection Sensitizes Human Hepatocytes to TRAIL-Induced Apoptosis in a Caspase 9-Dependent Manner1

Hepatitis C Virus Infection Sensitizes Human Hepatocytes to ...

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第五届国际暨全国肝衰竭与人工肝学术会议

作者： Seb.stian Gorke Sib.lle J.Rau mirjam b.zeisel Eb.rhard Hildt Kiyoshi Himmelsb.ch Monica Carvajal-Yepes Roman Hub.r Takaji Wakita Annette Schmitt-Craeff Cathy Royer Hub.rt E.b.um Richard Fischer Thomas F.b.umert Department of infectious disease Southwest hospital of Third Military Medical University

＜正＞Apoptosis of infected cells represents a key host defense mechanism against viral *** impact of apoptosis on the elimination of hepatitis C virus（HCV）-infected cells is poorly *** TRAIL has b.en implicated in ...

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