Cells transfected with human interleukin 6 cDNA acquire binding sites for the hepatitis B virus envelope protein.
Earlier studies revealed that human interleukin 6 (IL-6) contains recognition sites for the hepatitis B virus (HBV) envelope (env) protein, and that IL-6 and anti-IL-6 antibodies, respectively, inhibited the interaction of cells expressing a receptor for HBV with the preS(21-47) segment of the HBV env protein, encompassing the complementary attachment site for IL-6. This suggested that IL-6 mediates HBV-cell interactions. We report that: (a) Chinese hamster ovary cells transfected with human IL-6 cDNA and Spodoptera frugiperda ovarian insect cells infected with recombinant baculovirus carrying human IL-6 cDNA expressed receptors for the preS(21-47) region of the HBV env protein, indicating that expression of IL-6 on the surface of cells is sufficient to endow them with receptors for HBV. (b) Among peptides covering the entire sequence of human IL-6 and the corresponding antipeptide antibodies, the peptide IL-6[35-66] and anti-IL-6[35-66] most effectively inhibited the interaction between human hepatoma HepG2 cells and the preS(21-47) ligand, suggesting that this region of the human IL-6 sequence encompasses a binding site for the HBV env protein. (c) Studies with replacement set peptides from the preS(21-47) sequence indicated that residues 21-25, 28, 31, 33-35, 39, and 43-45 can be replaced by alanine (serine) residues, while all the other residues are essential for maintaining the cell receptor/IL-6 binding activity. Further delineation of complementary sites on IL-6 and on the HBV env protein may contribute to the design of compounds inhibiting HBV replication.
Neurath
A R
AR
Lindsley F. Kimball Research Institute, New York Blood Center, New York 10021.
Strick
N
N
Li
Y Y
YY
D000595:Amino Acid Sequence; D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D001665:Binding Sites; D016466:CHO Cells; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D006224:Cricetinae; D004247:DNA / Q000235:genetics*; D015686:Gene Products, env / Q000378:metabolism*; D006515:Hepatitis B virus / Q000378:metabolism*; D006801:Humans; D007106:Immune Sera; D015151:Immunoblotting; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms; D008969:Molecular Sequence Data; D009036:Moths; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D015686:Gene Products, env; D007106:Immune Sera; D015850:Interleukin-6; D010455:Peptides; D004247:DNA