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 vir...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 about 20%-30% of acutely infected individuals and results in resolution of infection without sequaelae. Both viral and host factors appear to play an important role for resolution of acute infection. A large body of evidence suggests that a strong, multispecific and long-lasting cellular immune response appears to be 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 been less defined. In recent years, the development of robust tissue culture model systems for HCV entry and infection has finally allowed study of antibody-mediated neutralization and to gain further insights into viral targets of host neutralizing responses. In addition, detailed analysis of antibody-mediated neutralization in individual patients as well as cohorts with well defined viral isolates has enabled the study of neutralizing responses in the course of HCV infection and characterization of the impact of neutralizing antibodiesfor control of viral infection. This review will summarize recent progress in the understanding of the molecular mechanisms of antibody-mediated neutralization and its impact for HCV pathogenesis.展开更多
The majority of individuals exposed to hepatitis C virus(HCV) establish a persistent infection,which is a leading cause of chronic liver disease,cirrhosis and hepatocellular carcinoma.Major progress has been made duri...The majority of individuals exposed to hepatitis C virus(HCV) establish a persistent infection,which is a leading cause of chronic liver disease,cirrhosis and hepatocellular carcinoma.Major progress has been made during the past twenty-five years in understanding the HCV life cycle and immune responses against HCV infection.Increasing evidence indicates that host genetic factors can significantly influence the outcome of HCV infection and the response to interferon alpha-based antiviral therapy.The arrival of highly effective and convenient treatment regimens for patients chronically infected with HCV has improved prospects for the eradication of HCV worldwide.Clinical trials are evaluating the best anti-viral drug combination,treatment doses and duration.The new treatments are better-tolerated and have shown success rates of more than 95%.However,the recent breakthrough in HCV treatment raises new questions and challenges,including the identification of HCVinfected patients and to link them to appropriate health care,the high pricing of HCV drugs,the emergence of drug resistance or naturally occurring polymorphism in HCV sequences which can compromise HCV treatment response.Finally,we still do not have a vaccine against HCV.In this concise review,we will highlight the progress made in understanding HCV infection and therapy.We will focus on the most significant unsolved problems and the key future challenges in the management of HCV infection.展开更多
基金Inserm, France Université Louis Pasteur, France+3 种基金the European Union (Virgil Network of Excellence)the DeutscheForschungsgemeinschaft (Ba1417/11-1), Germanythe ANRchair of excellence program and ANRS, FranceInserm "PosteVert" research fellowship in the framework of Inserm EuropeanAssociated Laboratory Inserm U748-Department of Medicine Ⅱ,University of Freiburg, Germany
文摘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 about 20%-30% of acutely infected individuals and results in resolution of infection without sequaelae. Both viral and host factors appear to play an important role for resolution of acute infection. A large body of evidence suggests that a strong, multispecific and long-lasting cellular immune response appears to be 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 been less defined. In recent years, the development of robust tissue culture model systems for HCV entry and infection has finally allowed study of antibody-mediated neutralization and to gain further insights into viral targets of host neutralizing responses. In addition, detailed analysis of antibody-mediated neutralization in individual patients as well as cohorts with well defined viral isolates has enabled the study of neutralizing responses in the course of HCV infection and characterization of the impact of neutralizing antibodiesfor control of viral infection. This review will summarize recent progress in the understanding of the molecular mechanisms of antibody-mediated neutralization and its impact for HCV pathogenesis.
文摘The majority of individuals exposed to hepatitis C virus(HCV) establish a persistent infection,which is a leading cause of chronic liver disease,cirrhosis and hepatocellular carcinoma.Major progress has been made during the past twenty-five years in understanding the HCV life cycle and immune responses against HCV infection.Increasing evidence indicates that host genetic factors can significantly influence the outcome of HCV infection and the response to interferon alpha-based antiviral therapy.The arrival of highly effective and convenient treatment regimens for patients chronically infected with HCV has improved prospects for the eradication of HCV worldwide.Clinical trials are evaluating the best anti-viral drug combination,treatment doses and duration.The new treatments are better-tolerated and have shown success rates of more than 95%.However,the recent breakthrough in HCV treatment raises new questions and challenges,including the identification of HCVinfected patients and to link them to appropriate health care,the high pricing of HCV drugs,the emergence of drug resistance or naturally occurring polymorphism in HCV sequences which can compromise HCV treatment response.Finally,we still do not have a vaccine against HCV.In this concise review,we will highlight the progress made in understanding HCV infection and therapy.We will focus on the most significant unsolved problems and the key future challenges in the management of HCV infection.
