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Journal of Virology, April 2007, p. 3933-3941, Vol. 81, No. 8
0022-538X/07/$08.00+0     doi:10.1128/JVI.02622-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Sulfated Homologues of Heparin Inhibit Hepatitis C Virus Entry into Mammalian Cells{triangledown}

Arnab Basu,1,{dagger} Tatsuo Kanda,2 Aster Beyene,1 Kousuke Saito,1 Keith Meyer,1 and Ranjit Ray1,3*

Departments of Internal Medicine,1 Pathology,2 Molecular Microbiology and Immunology, Saint Louis University, St. Louis, Missouri3

Received 28 November 2006/ Accepted 23 January 2007

The mechanism of entry of hepatitis C virus (HCV) through interactions between the envelope glycoproteins and specific cell surface receptors remains unclear at this time. We have previously shown with the vesicular stomatitis virus (VSV)/HCV pseudotype model that the hypervariable region 1 of the HCV E2 envelope glycoprotein helps in binding with glycosaminoglycans present on the cell surface. In this study, we have examined the binding of HCV envelope glycoproteins with chemically modified derivatives of heparin. Furthermore, we have determined the functional relevance of the interaction of heparin derivatives with HCV envelope glycoproteins for infectivity by using a human immunodeficiency virus (HIV)/HCV pseudotype, a VSV/HCV pseudotype, and cell culture-grown HCV genotype 1a. Taken together, our results suggest that the HCV envelope glycoproteins rely upon O-sulfated esters of a heparin homologue to facilitate entry into mammalian cells.


* Corresponding author. Mailing address: Division of Infectious Diseases & Immunology, Department of Internal Medicine, Saint Louis University, 3635 Vista Ave., FDT-8N, St. Louis, MO 63110. Phone: (314) 577-8648. Fax: (314) 771-3816. E-mail: rayr{at}slu.edu

{triangledown} Published ahead of print on 7 February 2007.

{dagger} Present address: Microbiotix, Inc., One Innovation Dr., Worcester, MA 01605.


Journal of Virology, April 2007, p. 3933-3941, Vol. 81, No. 8
0022-538X/07/$08.00+0     doi:10.1128/JVI.02622-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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Copyright © 2007 by the American Society for Microbiology. All rights reserved.