Glucocorticosteroids increase cell entry by hepatitis C virus

Gastroenterology. 2010 May;138(5):1875-84. doi: 10.1053/j.gastro.2010.02.004. Epub 2010 Feb 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Genotype
  • Glucocorticoids / antagonists & inhibitors
  • Glucocorticoids / pharmacology*
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepacivirus / pathogenicity
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Hepatocytes / virology
  • Hormone Antagonists / pharmacology
  • Humans
  • Immunosuppressive Agents / antagonists & inhibitors
  • Immunosuppressive Agents / pharmacology*
  • Membrane Proteins / genetics
  • Mifepristone / pharmacology
  • Occludin
  • Prednisolone / antagonists & inhibitors
  • Prednisolone / pharmacology*
  • RNA, Messenger / metabolism
  • RNA, Viral / biosynthesis
  • Scavenger Receptors, Class B / genetics
  • Time Factors
  • Virus Internalization / drug effects*
  • Virus Replication / drug effects


  • Glucocorticoids
  • Hormone Antagonists
  • Immunosuppressive Agents
  • Membrane Proteins
  • OCLN protein, human
  • Occludin
  • RNA, Messenger
  • RNA, Viral
  • SCARB1 protein, human
  • Scavenger Receptors, Class B
  • Mifepristone
  • Prednisolone