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Identification and Characterization of Peptides That Interact with Hepatitis B Virus via the Putative Receptor Binding Site

State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China,¹ Unité de Pathogenese des Hépatites Virales B et Immunothérapie, INSERM U812/Institut Pasteur, 75724 Paris, France,² Ruijin Hospital, Department of Infectious Diseases, Shanghai 200025, China,³ Unité Postulante des Hépacivirus, Institut Pasteur, 75724 Paris, France,⁴ Unité d'Organisation Nucléaire et Oncogénèse, INSERM U579/Institut Pasteur, 75724 Paris, France⁵

Received 16 June 2006/ Accepted 30 November 2006

A direct involvement of the PreS domain of the hepatitis B virus (HBV) large envelope protein, and in particular amino acid residues 21 to 47, in virus attachment to hepatocytes has been suggested by many previous studies. Several PreS-interacting proteins have been identified. However, they share few common sequence motifs, and a bona fide cellular receptor for HBV remains elusive. In this study, we aimed to identify PreS-interacting motifs and to search for novel HBV-interacting proteins and the long-sought receptor. PreS fusion proteins were used as baits to screen a phage display library of random peptides. A group of PreS-binding peptides were obtained. These peptides could bind to amino acids 21 to 47 of PreS1 and shared a linear motif (W₁T₂X₃W₄W₅) sufficient for binding specifically to PreS and viral particles. Several human proteins with such a motif were identified through BLAST search. Analysis of their biochemical and structural properties suggested that lipoprotein lipase (LPL), a key enzyme in lipoprotein metabolism, might interact with PreS and HBV particles. The interaction of HBV with LPL was demonstrated by in vitro binding, virus capture, and cell attachment assays. These findings suggest that LPL may play a role in the initiation of HBV infection. Identification of peptides and protein ligands corresponding to LPL that bind to the HBV envelope will offer new therapeutic strategies against HBV infection.

Published ahead of print on 27 December 2006.

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• Blanchet, M., Sureau, C. (2007). Infectivity Determinants of the Hepatitis B Virus Pre-S Domain Are Confined to the N-Terminal 75 Amino Acid Residues. J. Virol. 81: 5841-5849 [Abstract] [Full Text]