HIV-1 Glycoprotein 41 Ectodomain Induces Activation of the CD74 Protein-mediated Extracellular Signal-regulated Kinase/Mitogen-activated Protein Kinase Pathway to Enhance Viral Infection*
HIV-1 Glycoprotein 41 Ectodomain Induces Activation of the CD74 Protein-mediated Extracellular Signal-regulated Kinase/Mitogen-activated Protein Kinase Pathway to Enhance Viral Infection*
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DOI：
10.1074/jbc.m111.267393
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发表时间：
2011-10
期刊：
影响因子：
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通讯作者：
C. Zhou;Lu Lu-Lu;Suiyi Tan;Shibo Jiang;Ying-hua Chen
中科院分区：
文献类型：
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作者：
C. Zhou;Lu Lu-Lu;Suiyi Tan;Shibo Jiang;Ying-hua Chen
除了介导病毒进入过程外，人类免疫缺陷病毒 (HIV-1) 包膜蛋白 gp41 还可以与许多宿主细胞成分结合并调节细胞功能。使用酵母双杂交系统，我们筛选了人骨髓 cDNA 文库，并鉴定了一种新型 gp41 结合蛋白 CD74（MHC II 类相关不变链）。在这里，我们报告了 gp41 和 CD74 之间相互作用介导的可能的生物效应。我们发现HIV-1 gp41可以直接与HIV-1感染细胞中的宿主CD74结合，而源自gp41环区（aa 597-611）的肽6358可以有效阻断gp41-CD74相互作用。由于这种结合，重组可溶性 gp41 和 gp41 肽 6358 激活了 CD74 介导的 ERK/MAPK 途径，并显着增强了体外 HIV-1 感染。相反，重组CD74胞外结构域可以抑制增强作用。这些结果揭示了 gp41 介导 HIV-1 感染和复制的新机制。
Besides mediating the viral entry process, the human immunodeficiency virus (HIV-1) envelope protein gp41 can bind to many host cell components and regulate cell functions. Using a yeast two-hybrid system, we screened a human bone marrow cDNA library and identified a novel gp41-binding protein, CD74 (the MHC class II-associated invariant chain). Here, we report possible biological effects mediated by interaction between gp41 and CD74. We found that HIV-1 gp41 could bind directly to host CD74 in HIV-1-infected cells, and the peptide 6358 derived from gp41 loop region (aa 597–611) could effectively block the gp41-CD74 interaction. As a result of this binding, recombinant soluble gp41 and gp41 peptide 6358 activated the CD74-mediated ERK/MAPK pathway and significantly enhanced HIV-1 infection in vitro. Conversely, the enhancing effect could be suppressed by the recombinant CD74 extracellular domain. These results reveal a novel mechanism underlying gp41 mediation of HIV-1 infection and replication.