2.50
Hdl Handle:
http://hdl.handle.net/10033/107619
Title:
Glucocorticosteroids increase cell entry by hepatitis C virus.
Authors:
Ciesek, Sandra; Steinmann, Eike; Iken, Markus; Ott, Michael; Helfritz, Fabian A; Wappler, Ilka; Manns, Michael P; Wedemeyer, Heiner; Pietschmann, Thomas
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.
Affiliation:
Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany.
Citation:
Glucocorticosteroids increase cell entry by hepatitis C virus. 2010, 138 (5):1875-84 Gastroenterology
Journal:
Gastroenterology
Issue Date:
May-2010
URI:
http://hdl.handle.net/10033/107619
DOI:
10.1053/j.gastro.2010.02.004
PubMed ID:
20152835
Type:
Article
Language:
en
ISSN:
1528-0012
Appears in Collections:
publications of the department experimental Virology([TC]EVIR)

Full metadata record

DC FieldValue Language
dc.contributor.authorCiesek, Sandraen
dc.contributor.authorSteinmann, Eikeen
dc.contributor.authorIken, Markusen
dc.contributor.authorOtt, Michaelen
dc.contributor.authorHelfritz, Fabian Aen
dc.contributor.authorWappler, Ilkaen
dc.contributor.authorManns, Michael Pen
dc.contributor.authorWedemeyer, Heineren
dc.contributor.authorPietschmann, Thomasen
dc.date.accessioned2010-07-14T09:43:57Z-
dc.date.available2010-07-14T09:43:57Z-
dc.date.issued2010-05-
dc.identifier.citationGlucocorticosteroids increase cell entry by hepatitis C virus. 2010, 138 (5):1875-84 Gastroenterologyen
dc.identifier.issn1528-0012-
dc.identifier.pmid20152835-
dc.identifier.doi10.1053/j.gastro.2010.02.004-
dc.identifier.urihttp://hdl.handle.net/10033/107619-
dc.description.abstractBACKGROUND & 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.en
dc.language.isoenen
dc.subject.meshCells, Cultureden
dc.subject.meshDose-Response Relationship, Drugen
dc.subject.meshGenotypeen
dc.subject.meshGlucocorticoidsen
dc.subject.meshHepacivirusen
dc.subject.meshHepatocytesen
dc.subject.meshHormone Antagonistsen
dc.subject.meshHumansen
dc.subject.meshImmunosuppressive Agentsen
dc.subject.meshMembrane Proteinsen
dc.subject.meshMifepristoneen
dc.subject.meshPrednisoloneen
dc.subject.meshRNA, Messengeren
dc.subject.meshRNA, Viralen
dc.subject.meshScavenger Receptors, Class Ben
dc.subject.meshTime Factorsen
dc.subject.meshVirus Internalizationen
dc.subject.meshVirus Replicationen
dc.titleGlucocorticosteroids increase cell entry by hepatitis C virus.en
dc.typeArticleen
dc.contributor.departmentDepartment of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany.en
dc.identifier.journalGastroenterologyen

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