Cells transfected with human interleukin 6 cDNA acquire binding sites for the hepatitis B virus envelope protein.
Cells transfected with human interleukin 6 cDNA acquire binding sites for the hepatitis B virus envelope protein.
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DOI：
10.1084/jem.176.6.1561
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发表时间：
1992-12-01
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早期的研究表明，人白细胞介素6 （IL-6）含有乙型肝炎病毒（HBV）包膜（env）蛋白的识别位点，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）片段的相互作用，该片段包含IL-6的互补附着位点。这表明IL-6介导hbv -细胞相互作用。我们报道：(a)转染了人IL-6 cDNA的中国仓鼠卵巢细胞和转染了携带人IL-6 cDNA的重组杆状病毒的frugiperda卵巢昆虫细胞表达了HBV env蛋白preS（21-47）区域的受体，表明细胞表面IL-6的表达足以赋予它们HBV受体。(b)在覆盖人IL-6整个序列和相应的抗肽抗体的多肽中，肽IL-6[35-66]和抗IL-6[35-66]最有效地抑制人肝癌HepG2细胞与preS（21-47）配体之间的相互作用，这表明人IL-6序列的这一区域包含HBV env蛋白的结合位点。(c)对preS（21-47）序列的替代肽的研究表明，残基21-25、28、31、33-35、39和43-45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的结合活性都是必需的。进一步描述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。
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.