Dissecting the role of putative CD81 binding regions of E2 in mediating HCV entry Putative CD81 binding region 1 is not involved in CD81 binding.docVIP

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Dissecting the role of putative CD81 binding regions of E2 in mediating HCV entry Putative CD81 binding region 1 is not involved in CD81 binding.doc

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Dissecting the role of putative CD81 binding regions of E2 in mediating HCV entry Putative CD81 binding region 1 is not involved in CD81 binding

Virology Journal BioMedCentral Research Open Access Dissecting the role of putative CD81 binding regions of E2 in mediating HCV entry: Putative CD81 binding region 1 is not involved in CD81 binding Katharina B Rothwangl1, Balaji Manicassamy1,3, Susan L Uprichard1,2 and Lijun Rong*1 Address: 1Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA, 2Department of Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA and 3Mount Sinai School of Medicine, 1 Gustave L. Levy Place, Box 1124 New York, NY 10029, USA Email: Katharina B Rothwangl - Katharin@; Balaji Manicassamy - Balaji.manicassamy@; Susan L Uprichard - Sluprich@; Lijun Rong* - lijun@ * Corresponding author Published: 20 March 2008 Received: 24 December 2007 Accepted: 20 March 2008 Virology Journal 2008, 5:46 doi:10.1186/1743-422X-5-46 This article is available from: /content/5/1/46 ? 2008 Rothwangl et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Hepatitis C virus (HCV) encodes two transmembrane glycoproteins E1 and E2 which form a heterodimer. E1 is believed to mediate fusion while E2 has been shown to bind cellular receptors including CD81. In this study, alanine substitutions in E2 were generated within putative CD81 binding regions to define residues critical for viral entry. The effect of each mutation was tested by challenging susceptible cell lines with mutant HCV E1E2 pseudotyped viruses generated using a lentiviral system (HCVpp). In addition to assaying infectivity, producer cell expression and HCVpp incorporation of HCV E1 and E2 proteins, CD81 binding profiles, and E1E2 association of muta