Rizzuto C D, Wyatt R, Hernández-Ramos N, Sun Y, Kwong P D, Hendrickson W A, Sodroski J
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Science. 1998 Jun 19;280(5371):1949-53. doi: 10.1126/science.280.5371.1949.
The entry of primate immunodeficiency viruses into target cells depends on a sequential interaction of the gp120 envelope glycoprotein with the cellular receptors, CD4 and members of the chemokine receptor family. The gp120 third variable (V3) loop has been implicated in chemokine receptor binding, but the use of the CCR5 chemokine receptor by diverse primate immunodeficiency viruses suggests the involvement of an additional, conserved gp120 element. Through the use of gp120 mutants, a highly conserved gp120 structure was shown to be critical for CCR5 binding. This structure is located adjacent to the V3 loop and contains neutralization epitopes induced by CD4 binding. This conserved element may be a useful target for pharmacologic or prophylactic intervention in human immunodeficiency virus (HIV) infections.
灵长类免疫缺陷病毒进入靶细胞取决于糖蛋白120(gp120)包膜糖蛋白与细胞受体CD4和趋化因子受体家族成员的顺序相互作用。gp120的第三个可变(V3)环与趋化因子受体结合有关,但多种灵长类免疫缺陷病毒对CCR5趋化因子受体的利用表明,gp120还有一个额外的保守元件参与其中。通过使用gp120突变体,已证明一种高度保守的gp120结构对CCR5结合至关重要。该结构位于V3环附近,包含由CD4结合诱导的中和表位。这一保守元件可能是人类免疫缺陷病毒(HIV)感染药物或预防性干预的有用靶点。