Constitutive cell surface association between CD4 and CCR5.
Constitutive cell surface association between CD4 and CCR5.
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DOI：
10.1073/pnas.96.13.7496
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发表时间：
1999-06
影响因子：
11.1
通讯作者：
Xiaodong Xiao;Lijun Wu;T. Stantchev;Yan‐Ru Feng;S. Ugolini;H. Chen;Zhimin Shen;J. Riley;C. Bro
中科院分区：
文献类型：
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作者：
Xiaodong Xiao;Lijun Wu;T. Stantchev;Yan‐Ru Feng;S. Ugolini;H. Chen;Zhimin Shen;J. Riley;C. Bro
HIV-1进入细胞涉及病毒包膜糖蛋白（Env）的gp 120、受体（CD 4）和辅助受体之间的复合物的形成。对于大多数HIV病毒株，这种辅助受体是CCR 5。在这里，我们提供的证据表明，CD 4特异性与CCR 5在gp 120或任何其他受体特异性配体的情况下。与CCR 5共免疫沉淀的CD 4的量显著高于与其他主要HIV共受体CXCR 4的量，并且与CXCR 4相反，CD 4-CCR 5共免疫沉淀没有被gp 120显著增加。CD 4-CCR 5相互作用可能通过CCR 5的第二胞外环和CD 4的前两个结构域进行。它可以被干扰HIV-1感染的CCR 5和CD 4特异性抗体抑制，表明可能在病毒进入中起作用。这些发现表明HIV-1进化和免疫致病性发展的可能途径，抗逆转录病毒药物的潜在新靶点和基于Env-CD 4-CCR 5复合物的疫苗开发工具。七跨膜结构域G蛋白偶联受体与另一种受体的组成性关联也表明了细胞表面受体之间串扰的新可能性。
HIV-1 entry into cells involves formation of a complex between gp120 of the viral envelope glycoprotein (Env), a receptor (CD4), and a coreceptor. For most strains of HIV, this coreceptor is CCR5. Here, we provide evidence that CD4 is specifically associated with CCR5 in the absence of gp120 or any other receptor-specific ligand. The amount of CD4 coimmunoprecipitated with CCR5 was significantly higher than that with the other major HIV coreceptor, CXCR4, and in contrast to CXCR4 the CD4-CCR5 coimmunoprecipitation was not significantly increased by gp120. The CD4-CCR5 interaction probably takes place via the second extracellular loop of CCR5 and the first two domains of CD4. It can be inhibited by CCR5- and CD4-specific antibodies that interfere with HIV-1 infection, indicating a possible role in virus entry. These findings suggest a possible pathway of HIV-1 evolution and development of immunopathogenicity, a potential new target for antiretroviral drugs and a tool for development of vaccines based on Env-CD4-CCR5 complexes. The constitutive association of a seven-transmembrane-domain G protein-coupled receptor with another receptor also indicates new possibilities for cross-talk between cell surface receptors.