猴免疫缺陷病毒糖蛋白120不依赖CD4与恒河猴CCR5的结合

CD4-independent binding of SIV gp120 to rhesus CCR5.

作者信息

Martin K A, Wyatt R, Farzan M, Choe H, Marcon L, Desjardins E, Robinson J, Sodroski J, Gerard C, Gerard N P

机构信息

Perlmutter Laboratory, Children's Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.

出版信息

Science. 1997 Nov 21;278(5342):1470-3. doi: 10.1126/science.278.5342.1470.

DOI:10.1126/science.278.5342.1470

PMID:9367961

Abstract

CCR5 and CD4 are coreceptors for immunodeficiency virus entry into target cells. The gp120 envelope glycoprotein from human immunodeficiency virus strain HIV-1(YU2) bound human CCR5 (CCR5hu) or rhesus macaque CCR5 (CCR5rh) only in the presence of CD4. The gp120 from simian immunodeficiency virus strain SIVmac239 bound CCR5rh without CD4, but CCR5hu remained CD4-dependent. The CD4-independent binding of SIVmac239 gp120 depended on a single amino acid, Asp13, in the CCR5rh amino-terminus. Thus, CCR5-binding moieties on the immunodeficiency virus envelope glycoprotein can be generated by interaction with CD4 or by direct interaction with the CCR5 amino-terminus. These results may have implications for the evolution of receptor use among lentiviruses as well as utility in the development of effective intervention.

摘要

CCR5和CD4是免疫缺陷病毒进入靶细胞的共受体。来自人类免疫缺陷病毒1型（HIV-1）（YU2）株的gp120包膜糖蛋白仅在存在CD4的情况下与人CCR5（CCR5hu）或恒河猴CCR5（CCR5rh）结合。来自猴免疫缺陷病毒SIVmac239株的gp120在没有CD4的情况下与CCR5rh结合，但CCR5hu仍然依赖CD4。SIVmac239 gp120的不依赖CD4的结合取决于CCR5rh氨基末端的单个氨基酸Asp13。因此，免疫缺陷病毒包膜糖蛋白上的CCR5结合部分可以通过与CD4相互作用或通过与CCR5氨基末端直接相互作用产生。这些结果可能对慢病毒之间受体使用的进化以及有效干预措施开发中的效用有影响。