Loading...
Glucocorticosteroids increase cell entry by hepatitis C virus.
Ciesek, Sandra Iken, Markus Ott, Michael Helfritz, Fabian A Wappler, Ilka Manns, Michael P Wedemeyer, Heiner Pietschmann, Thomas
Ciesek, Sandra
Iken, Markus
Ott, Michael
Helfritz, Fabian A
Wappler, Ilka
Manns, Michael P
Wedemeyer, Heiner
Pietschmann, Thomas
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
2010-05
Submitted date
Files
Loading...
original manuscript
Adobe PDF, 938.74 KB
Other Titles
Abstract
BACKGROUND & AIMS: Corticosteroids are used as immunosuppressants in patients with autoimmune 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-7.5 cells and primary human hepatocytes using cell culture- and patient-derived HCV. Replication was quantified by immunofluorescence, luciferase assays, quantitative reverse-transcriptase polymerase 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 stomatitis 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-2 host cell proteins required for HCV infection; increase of entry by glucocorticosteroids was ablated by RU-486, an inhibitor of glucocorticosteroid signaling. 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 high-dose glucocorticosteroids on HCV infection in vivo may be due to increased HCV dissemination.
Citation
Glucocorticosteroids increase cell entry by hepatitis C virus. 2010, 138 (5):1875-84 Gastroenterology
Publisher
Journal
PubMed ID
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
en
Description
Series/Report no.
ISSN
1528-0012