Hepatitis C virus entry and glucocorticosteroids

[摘要] Background & Aims Corticosteroids are used as immunosuppressants in patients with autormmune disorders and transplant recipients However these drugs worsen hepatitis C virus (HCV) recurrence after liver transplantation suggesting that they may directly exacerbate HCV infection Methods The influence of immunosuppressive drugs on HCV replication assembly and entry was assessed in Huh-75 cells and primary human hepatocytes using cell culture- and patient-derived HCV Replication was quantified by immunofluorescence Iuciferase assays quantitative reverse-transcnptase polym erase chain reaction or core enzyme-linked immunosorbent assays Expression of HCV entry factors was evaluated by cell sorting and immunoblot analyses Results Glucocorticosteroids slightly reduced HCV RNA replication but increased efficiency of HCV entry by up to 10-fold This was independent of HCV genotype but specific to HCV because vesicular stoma= virus glycoprotein-dependent infection was not affected by these drugs The increase in HCV entry was accompanied by up-regulation of messenger RNA and protein levels of occludin and the scavenger receptor class B type I - two host cell proteins required for HCV infection increase of entry by glucocorticosteroids was ablated by RU-486 an inhibitor of glucocorticosteroid signalling Glucocorticosteroids increased propagation of cell culture-derived HCV approximately 5- to 10-fold in partially differentiated human hepatoma cells and increased infection of primary human hepatocytes by cell culture- and patient-derived HCV Conclusions Glucocorticosteroides specifically increase HCV entry by up-regulating the cell entry factors occludin and scavenger receptor class B type I Our data suggest that the potential effects of highdose glucocorticosteroids on HCV infection in vivo may be due to increased HCV dissemination (C) 2010 European Association for the Study of the Liver Published by Elsevier B V All rights reserved

[发布日期] 2010-12-01