Ultrastructural remodelling of e ndoplasmic reticulum-derived membranes and hepatitis C virus morphogenesis in human liver samples

[摘要] Introduction:hepatitis C virus infection is considered as a leading cause of liver diseaseworldwide. Despite recent advances in understanding the hepatitis C virus lifecycle using the highly replicative JFH1 strain in human hepatoma cells, littleis known about hepatitis C virus morphogenesis. Low levels of hepatitis C virusassembly in this cell culture model as well as low levels and complexity ofhepatitis C virus particles in infected humans and chimpanzees have hamperedthe study of hepatitis C virus morphogenesis in vivo.Objetivo: to study the ultrastructural features and viral assembly eventsin hepatocytes from HCV hepatitis C virus-infected patients. Methods: liver needle biopsies samples of patients with hepatitis C virusinfection, specific antibodies against hepatitis C virus and transmission electronmicroscopy and immunoelectron microscopy analyses were used in this study. Results: ultrastructural studies in liver biopsies from hepatitis C virus-infectedpatients revealed that hepatitis C virus infection was related with remodellingof endoplasmic reticulum-derived membranes and with a variety of cytoplasmicmicroenvironments in hepatocytes. Dilated endoplasmic reticulum and formationof various membrane vesicles are features that have been associated with theviral replication complex. Interestingly, hepatitis C virus-like particles andcore-like particles budding and assembly were observed near convoluted electron-densemembranes and tubular structures. Particularly, hepatitis C virus structuralproteins localize to the endoplasmic reticulum. Conclusions: these events indicate that hepatitis C virus nucleocapsidsand early virion assembly take place at endoplasmic reticulum membranes thatare associated with these cytoplasmic microenvironments in human hepatocytes.

[学科分类] 传染病学

[关键词] HCV;morphogenesis;viral replication;liver biopsies;viral assembly.