Structural mapping of CD134 residues critical for interaction with feline immunodeficiency virus
Structural mapping of CD134 residues critical for interaction with feline immunodeficiency virus
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DOI：
10.1038/nsmb872
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发表时间：
2005-01-01
影响因子：
16.8
通讯作者：
Elder, JH
中科院分区：
文献类型：
--
作者：
de Parseval, A;Chatterji, U;Elder, JH
CD134 是猫免疫缺陷病毒 (FIV) 的主要结合受体，与 CXCR4 一起促进 CD4(+) T 细胞的感染。人类 CD134 不支持 FIV 感染。为了描绘对于定义 CD134 病毒特异性重要的区域，我们在人类和猫科动物 CD134 之间交换了结构域。 FIV 表面糖蛋白 (SU) 的结合位点位于结构域 1 中，该区域不同于天然配体 (CD134L) 结合位点。诱变表明 Asp60 和 Asp62 是与 FIV 相互作用所必需的，并且建模研究将这两个残基定位于结构域 1 的外边缘。取代 S60D 和 N62D 与 H45S、R59G 和 V64K 结合，赋予 FIV SU 结合和人类 CD134 的受体功能。最后，我们证明可溶性CD134以类似于CD4增强HIV感染的方式促进CD134(-)CXCR4(+)靶细胞的感染。
CD134 is a primary binding receptor for feline immunodeficiency virus (FIV), and with CXCR4 facilitates infection of CD4(+) T cells. Human CD134 fails to support FIV infection. To delineate the regions important for defining virus specificity of CD134, we exchanged domains between human and feline CD134. The binding site for FIV surface glycoprotein (SU) is located in domain 1, in a region distinct from the natural ligand (CD134L)- binding site. Mutagenesis showed that Asp60 and Asp62 are required for interaction with FIV, and modeling studies localized these two residues to the outer edge of domain 1. Substitutions S60D and N62D, in conjunction with H45S, R59G and V64K, imparted both FIV SU binding and receptor function to human CD134. Finally, we demonstrated that soluble CD134 facilitates infection of CD134(-) CXCR4(+) target cells in a manner analogous to CD4 augmentation of HIV infection.