Virology and cell biology of the hepatitis C virus life cycle: an update.

Affiliations ECOFECTInternational audienceHepatitis C virus (HCV) is an important human pathogen that causes hepatitis, liver cirrhosis and hepatocellular carcinoma. It imposes a serious problem to public health in the world as the population of chronically infected HCV patients who are at risk of progressive liver disease is projected to increase significantly in the next decades. However, the arrival of new antiviral molecules is progressively changing the landscape of hepatitis C treatment. The search for new anti-HCV therapies has also been a driving force to better understand how HCV interacts with its host, and major progresses have been made on the various steps of the HCV life cycle. Here, we review the most recent advances in the fast growing knowledge on HCV life cycle and interaction with host factors and pathways

The Hepatitis C Virus Glycan Shield and Evasion of the Humoral Immune Response

Despite the induction of effective immune responses, 80% of hepatitis C virus (HCV)-infected individuals progress from acute to chronic hepatitis. In contrast to the cellular immune response, the role of the humoral immune response in HCV clearance is still subject to debate. Indeed, HCV escapes neutralizing antibodies in chronically infected patients and reinfection has been described in human and chimpanzee. Studies of antibody-mediated HCV neutralization have long been hampered by the lack of cell-culture-derived virus and the absence of a small animal model. However, the development of surrogate models and recent progress in HCV propagation in vitro now enable robust neutralization assays to be performed. These advances are beginning to shed some light on the mechanisms of HCV neutralization. This review summarizes the current state of knowledge of the viral targets of anti-HCV-neutralizing antibodies and the mechanisms that enable HCV to evade the humoral immune response. The recent description of the HCV glycan shield that reduces the immunogenicity of envelope proteins and masks conserved neutralizing epitopes at their surface constitutes the major focus of this review

Infectious Hepatitis C Virus Pseudo-particles Containing Functional E1–E2 Envelope Protein Complexes

The study of hepatitis C virus (HCV), a major cause of chronic liver disease, has been hampered by the lack of a cell culture system supporting its replication. Here, we have successfully generated infectious pseudo-particles that were assembled by displaying unmodified and functional HCV glycoproteins onto retroviral and lentiviral core particles. The presence of a green fluorescent protein marker gene packaged within these HCV pseudo-particles allowed reliable and fast determination of infectivity mediated by the HCV glycoproteins. Primary hepatocytes as well as hepato-carcinoma cells were found to be the major targets of infection in vitro. High infectivity of the pseudo-particles required both E1 and E2 HCV glycoproteins, and was neutralized by sera from HCV-infected patients and by some anti-E2 monoclonal antibodies. In addition, these pseudo-particles allowed investigation of the role of putative HCV receptors. Although our results tend to confirm their involvement, they provide evidence that neither LDLr nor CD81 is sufficient to mediate HCV cell entry. Altogether, these studies indicate that these pseudo-particles may mimic the early infection steps of parental HCV and will be suitable for the development of much needed new antiviral therapies

ALSACIA (Francia). 1:488400

Indica meridianos de origen: Isla del Hierro y París ; Márgenes graduados.Escala gráfica de 10 Lieues communes de 25 au Degré [= 9,1 cm], además en "Grandes lieues de 20 au Degré".Relieve representado mediante signos morfográfico

PROVENZA-COSTA AZUL (Francia). 1:564971

Indica meridianos de origen: Isla del Hierro y París ; Márgenes graduados.Escala gráfica además en 'Grandes lieves de France de 20 au Degré'.Indica relieve representado mediante signos morfográficos

LANGUEDOC (Francia). 1:266666

Indica meridianos de origen: Isla del Hierro y París ; Márgenes graduados.Escala gráfica además en 'Grandes lieves de 20 au Degré'.Indica relieve representado mediante signos morfográficos

NORTE (Francia) (Región). 1:352733

Indica meridianos de origen: Isla del Hierro y París ; Márgenes graduados.Escala gráfica además en 'Grandes Lieves de 20 au Degré'