Human immunodeficiency virus type 1 Vpu protein interacts with CD74 and modulates major histocompatibility complex class II presentation
Human immunodeficiency virus type 1 Vpu protein interacts with CD74 and modulates major histocompatibility complex class II presentation
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DOI：
10.1128/jvi.01373-07
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发表时间：
2008-01-01
影响因子：
5.4
通讯作者：
Jameel, Shahid
中科院分区：
文献类型：
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作者：
Hussain, Amjad;Wesley, Clement;Jameel, Shahid
人类免疫缺陷病毒1型(HIV-1)VPU辅助蛋白是一种跨膜蛋白，它下调CD4的表达并促进新病毒粒子的释放。我们筛选了一个人白细胞特异性酵母双杂交表达文库，以发现新的与VPU相互作用的细胞蛋白。主要组织相容性复合体II类(MHC II)不变链，也称为II或CD74，被发现就是这样的一种蛋白质。我们通过酵母双杂交试验和来自HIV-1感染细胞的免疫共沉淀显示了VPU和CD74的直接结合。VPU的细胞质区域与CD74的30个氨基酸的胞质尾部相互作用。感染野生型或VPU缺陷型HIV-1的人单核细胞U937细胞和转基因细胞显示VPU下调成熟MHC II分子的表面表达。细胞表面成熟MHC II分子的减少与培养中T细胞的抗原呈递减少有关。因此，VPU蛋白还通过减弱HIV感染期间的免疫反应而有助于病毒的持久性。这份报告进一步说明了艾滋病毒在免疫逃避中表现出的丰富多样性和冗余性。
The human immunodeficiency virus type 1 (HIV-1) Vpu accessory protein is a transmembrane protein that down regulates CD4 expression and promotes the release of new virions. We screened a human leukocyte-specific yeast two-hybrid expression library to discover novel Vpu-interacting cellular proteins. The major histocompatibility complex class II (MHC II) invariant chain, also called Ii or CD74, was found to be one such protein. We show direct binding of Vpu and CD74 by using a yeast two-hybrid assay and coimmunoprecipitation from HIV-1-infected cells. The cytoplasmic region of Vpu was found to interact with the 30-amino-acid cytoplasmic tail of CD74. Human monocytic U937 cells infected with wild-type or Vpu-defective HIV-1 and transfected cells showed that Vpu down modulated the surface expression of mature MHC II molecules. The reduction in cell surface mature MHC II molecules correlated with decreased antigen presentation to T cells in culture. Thus, the Vpu protein also contributes to viral persistence by attenuating immune responses during HIV infection. This report further exemplifies the rich diversity and redundancy shown by HIV in immune evasion.