Neurath A R, Strick N, Li Y Y
Lindsley F. Kimball Research Institute, New York Blood Center, New York 10021.
J Exp Med. 1992 Dec 1;176(6):1561-9. doi: 10.1084/jem.176.6.1561.
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.
早期研究表明，人白细胞介素6（IL-6）含有与乙型肝炎病毒（HBV）包膜（env）蛋白质的识别位点，并且IL-6和抗IL-6抗体分别抑制表达 HBV 受体的细胞与 HBV env 蛋白的 preS(21-47)片段之间的相互作用，该片段包含IL-6的互补结合位点。这表明IL-6介导HBV与细胞的相互作用。我们报告如下：（a）用人类IL-6 cDNA转染的中国仓鼠卵巢细胞和感染携带人类IL-6 cDNA的重组杆状病毒的草地贪夜蛾卵巢昆虫细胞表达了针对HBV env蛋白preS(21-47)区域的受体，这表明细胞表面IL-6的表达足以使其具有HBV受体。（b）在覆盖人类IL-6整个序列的肽段及相应的抗肽抗体中，肽段IL-6[35-66]和抗IL-6[35-66]最有效地抑制了人肝癌HepG2细胞与preS(21-47)配体之间的相互作用，这表明人类IL-6序列的该区域包含一个HBV env蛋白的结合位点。（c）对preS(21-47)序列的替换肽段研究表明，第21-25、28、31、33-35、39和43-45位残基可以被丙氨酸（丝氨酸）残基取代，而所有其他残基对于维持细胞受体/IL-6结合活性至关重要。进一步明确IL-6和HBV env蛋白上的互补位点可能有助于设计抑制HBV复制的化合物。
