公开(公告)号：US6057102A

公开(公告)日：2000-05-02

申请号：US907468

申请日：1997-08-08

申请人： Nathaniel R. Landau ,  Richard A. Koup ,  Rong Liu ,  William Paxton

发明人： Nathaniel R. Landau ,  Richard A. Koup ,  Rong Liu ,  William Paxton

IPC分类号： C07K14/715 ,  C12Q1/70 ,  C12Q1/68

CPC分类号： C12Q1/703 ,  C07K14/7158 ,  A01K2217/05 ,  C12Q2600/156

摘要： Entry of HIV-1 into target cells requires cell surface CD4 as well as additional host cell cofactors. A cofactor required for infection with virus adapted for growth in transformed T cell lines was recently identified and named fusin. Fusin, however, does not promote entry of macrophage-tropic viruses that are believed to be the key pathogenic strains in vivo. It has now been determined that the principal cofactor for entry mediated by the envelope glycoproteins of primary macrophage-tropic strains of HIV-1 is CC-CKR5, a receptor for the .beta.-chemokines RANTES, MIP-1.alpha., and MIP-1.beta.. It has also been found that individuals who are homozygous for a mutation of the CKR-5 receptor are resistent to HIV infection; in vitro infection requires a 1000-fold higher dose of HIV than normal cells. The mutation results in complete suppression of CKR-5 expression.

摘要翻译： HIV-1进入靶细胞需要细胞表面CD4以及额外的宿主细胞辅因子。 最近鉴定了一种在转化的T细胞系中适应生长的病毒感染所需的辅因子，并命名为fusin。 然而，Fusin不促进被认为是体内关键致病菌株的巨噬细胞 - 嗜性病毒的进入。 现在已经确定，由HIV-1的初级巨噬细胞 - 热带菌株的包膜糖蛋白引入的主要辅助因子是CC-CKR5，β-chemokines RANTES，MIP-1α和MIP-1β的受体 。 还发现对CKR-5受体的突变是纯合的个体对HIV感染是抗性的; 体外感染需要比正常细胞高1000倍的HIV。 突变导致CKR-5表达的完全抑制。