Smith D H, Byrn R A, Marsters S A, Gregory T, Groopman J E, Capon D J
Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080.
Science. 1987 Dec 18;238(4834):1704-7. doi: 10.1126/science.3500514.
The initial event in the infection of human T lymphocytes, macrophages, and other cells by human immunodeficiency virus (HIV-1) is the attachment of the HIV-1 envelope glycoprotein gp120 to its cellular receptor, CD4. As a step toward designing antagonists of this binding event, soluble, secreted forms of CD4 were produced by transfection of mammalian cells with vectors encoding versions of CD4 lacking its transmembrane and cytoplasmic domains. The soluble CD4 so produced binds gp120 with an affinity and specificity comparable to intact CD4 and is capable of neutralizing the infectivity of HIV-1. These studies reveal that the high-affinity CD4-gp120 interaction does not require other cell or viral components and may establish a novel basis for therapeutic intervention in the acquired immune deficiency syndrome (AIDS).
人类免疫缺陷病毒（HIV-1）感染人类T淋巴细胞、巨噬细胞和其他细胞的初始事件是HIV-1包膜糖蛋白gp120与其细胞受体CD4的结合。作为设计这种结合事件拮抗剂的一步，通过用编码缺失跨膜和胞质结构域的CD4变体的载体转染哺乳动物细胞，产生了可溶性、分泌形式的CD4。如此产生的可溶性CD4以与完整CD4相当的亲和力和特异性结合gp120，并能够中和HIV-1的感染性。这些研究表明，高亲和力的CD4-gp120相互作用不需要其他细胞或病毒成分，可能为获得性免疫缺陷综合征（AIDS）的治疗干预建立新的基础。
