Scavenger receptor class B type I is a key host factor for hepatitis C virus infection required for an entry step closely linked to CD81.

@article{citeulike:2364734, abstract = {Hepatitis C virus (HCV) is a major cause of chronic hepatitis worldwide. Scavenger receptor class B type I (SR-BI) has been shown to bind HCV envelope glycoprotein E2, participate in entry of HCV pseudotype particles, and modulate HCV infection. However, the functional role of SR-BI for productive HCV infection remains unclear. In this study, we investigated the role of SR-BI as an entry factor for infection of human hepatoma cells using cell culture-derived HCV (HCVcc). Anti-SR-BI antibodies directed against epitopes of the human SR-BI extracellular loop specifically inhibited HCVcc infection in a dose-dependent manner. Down-regulation of SR-BI expression by SR-BI-specific short interfering RNAs (siRNAs) markedly reduced the susceptibility of human hepatoma cells to HCVcc infection. Kinetic studies demonstrated that SR-BI acts predominately after binding of HCV at an entry step occurring at a similar time point as CD81-HCV interaction. Although the addition of high-density lipoprotein (HDL) enhanced the efficiency of HCVcc infection, anti-SR-BI antibodies and SR-BI-specific siRNA efficiently inhibited HCV infection independent of lipoprotein. Conclusion: Our data suggest that SR-BI (i) represents a key host factor for HCV entry, (ii) is implicated in the same HCV entry pathway as CD81, and (iii) targets an entry step closely linked to HCV-CD81 interaction.}, address = {Institut National de la Sant\'{e} et de la Recherche M\'{e}dicale (INSERM), U748, Strasbourg, France.}, author = {Zeisel, M. B. and Koutsoudakis, G. and Schnober, E. K. and Haberstroh, A. and Blum, H. E. and Cosset, F. L. and Wakita, T. and Jaeck, D. and Doffoel, M. and Royer, C. and Soulier, E. and Schvoerer, E. and Schuster, C. and Stoll-Keller, F. and Bartenschlager, R. and Pietschmann, T. and Barth, H. and Baumert, T. F. }, citeulike-article-id = {2364734}, doi = {http://dx.doi.org/10.1002/hep.21994}, issn = {1527-3350}, journal = {Hepatology}, month = {December}, number = {6}, pages = {1722--1731}, posted-at = {2008-02-12 03:43:37}, priority = {2}, title = {Scavenger receptor class B type I is a key host factor for hepatitis C virus infection required for an entry step closely linked to CD81.}, url = {http://dx.doi.org/10.1002/hep.21994}, volume = {46}, year = {2007} }

TY - JOUR ID - citeulike:2364734 L3 - citeulike-article-id:2364734 TI - Scavenger receptor class B type I is a key host factor for hepatitis C virus infection required for an entry step closely linked to CD81. JF - Hepatology VL - 46 IS - 6 SP - 1722 EP - 1731 AD - Institut National de la Santé et de la Recherche Médicale (INSERM), U748, Strasbourg, France. SN - 1527-3350 N2 - Hepatitis C virus (HCV) is a major cause of chronic hepatitis worldwide. Scavenger receptor class B type I (SR-BI) has been shown to bind HCV envelope glycoprotein E2, participate in entry of HCV pseudotype particles, and modulate HCV infection. However, the functional role of SR-BI for productive HCV infection remains unclear. In this study, we investigated the role of SR-BI as an entry factor for infection of human hepatoma cells using cell culture-derived HCV (HCVcc). Anti-SR-BI antibodies directed against epitopes of the human SR-BI extracellular loop specifically inhibited HCVcc infection in a dose-dependent manner. Down-regulation of SR-BI expression by SR-BI-specific short interfering RNAs (siRNAs) markedly reduced the susceptibility of human hepatoma cells to HCVcc infection. Kinetic studies demonstrated that SR-BI acts predominately after binding of HCV at an entry step occurring at a similar time point as CD81-HCV interaction. Although the addition of high-density lipoprotein (HDL) enhanced the efficiency of HCVcc infection, anti-SR-BI antibodies and SR-BI-specific siRNA efficiently inhibited HCV infection independent of lipoprotein. Conclusion: Our data suggest that SR-BI (i) represents a key host factor for HCV entry, (ii) is implicated in the same HCV entry pathway as CD81, and (iii) targets an entry step closely linked to HCV-CD81 interaction. AU - Zeisel, MB AU - Koutsoudakis, G AU - Schnober, EK AU - Haberstroh, A AU - Blum, HE AU - Cosset, FL AU - Wakita, T AU - Jaeck, D AU - Doffoel, M AU - Royer, C AU - Soulier, E AU - Schvoerer, E AU - Schuster, C AU - Stoll-Keller, F AU - Bartenschlager, R AU - Pietschmann, T AU - Barth, H AU - Baumert, TF PY - 2007/12// UR - http://dx.doi.org/10.1002/hep.21994 ER -