Identification and characterization of peptides that interact with hepatitis B virus via the putative receptor binding site.
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.
Deng
Qiang
Q
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, and Ruijin Hospital, Department of Infectious Diseases, Shanghai, China.
Zhai
Jian-wei
JW
Michel
Marie-Louise
ML
Zhang
Jun
J
Qin
Jun
J
Kong
Yu-ying
YY
Zhang
Xin-xin
XX
Budkowska
Agata
A
Tiollais
Pierre
P
Wang
Yuan
Y
Xie
You-hua
YH
D020816:Amino Acid Motifs; D001665:Binding Sites; D002460:Cell Line; D006514:Hepatitis B Surface Antigens / Q000378:metabolism*; D006515:Hepatitis B virus / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology*; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism*; D019151:Peptide Library; D011485:Protein Binding; D011498:Protein Precursors / Q000378:metabolism*; D011991:Receptors, Virus / Q000032:analysis* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D053585:Virus Attachment
D006514:Hepatitis B Surface Antigens; D019151:Peptide Library; D011498:Protein Precursors; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; C050806:presurface protein 1, hepatitis B surface antigen; D008071:Lipoprotein Lipase