Apolipoprotein E Mediates Attachment of Clinical Hepatitis C Virus to Hepatocytes by Binding to Cell Surface Heparan Sulfate Proteoglycan ReceptorsReportar como inadecuado




Apolipoprotein E Mediates Attachment of Clinical Hepatitis C Virus to Hepatocytes by Binding to Cell Surface Heparan Sulfate Proteoglycan Receptors - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Our previous studies demonstrated that the cell culture-grown hepatitis C virus of genotype 2a HCVcc uses apolipoprotein E apoE to mediate its attachment to the surface of human hepatoma Huh-7.5 cells. ApoE mediates HCV attachment by binding to the cell surface heparan sulfate HS which is covalently attached to the core proteins of proteoglycans HSPGs. In the present study, we further determined the physiological importance of apoE and HSPGs in the HCV attachment using a clinical HCV of genotype 1b HCV1b obtained from hepatitis C patients and human embryonic stem cell-differentiated hepatocyte-like cells DHHs. DHHs were found to resemble primary human hepatocytes. Similar to HCVcc, HCV1b was found to attach to the surface of DHHs by the apoE-mediated binding to the cell surface HSPGs. The apoE-specific monoclonal antibody, purified HSPGs, and heparin were all able to efficiently block HCV1b attachment to DHHs. Similarly, the removal of heparan sulfate from cell surface by treatment with heparinase suppressed HCV1b attachment to DHHs. More significantly, HCV1b attachment was potently inhibited by a synthetic peptide derived from the apoE receptor-binding region as well as by an HSPG-binding peptide. Likewise, the HSPG-binding peptide prevented apoE from binding to heparin in a dose-dependent manner, as determined by an in vitro heparin pull-down assay. Collectively, these findings demonstrate that HSPGs serve as major HCV attachment receptors on the surface of human hepatocytes to which the apoE protein ligand on the HCV envelope binds.



Autor: Jieyun Jiang, Xianfang Wu, Hengli Tang, Guangxiang Luo

Fuente: http://plos.srce.hr/



DESCARGAR PDF




Documentos relacionados