The Nef protein of human immunodeficiency virus establishes superinfection immunity by a dual strategy to downregulate cell-surface CCR5 and CD4
The Nef protein of human immunodeficiency virus establishes superinfection immunity by a dual strategy to downregulate cell-surface CCR5 and CD4
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DOI：
10.1016/j.cub.2005.02.058
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发表时间：
2005-04-26
期刊：
影响因子：
9.2
通讯作者：
Keppler, OT
中科院分区：
文献类型：
--
作者：
Michel, N;Allespach, I;Keppler, OT
背景：病毒经常使细胞对同一病毒的后续感染不敏感。这种状态的超感染免疫力抵消潜在的有害后果，为受感染的细胞，并促进高水平的复制和病毒传播的host.Results：在这里，我们表明，人类免疫缺陷病毒（HIV）采用其早期的基因产物Nef有效地干扰超感染的病毒进入步骤。在这种情况下，我们确定下调细胞表面CCR5，主要的HIV辅助受体，作为一种新的和高度保守的活动Nef。Nef通过不同的细胞机制靶向CCR5辅助受体和HIV结合受体CD4，以提高两种HIV受体组分的内吞速率并加速其降解。在功能上，这些遗传分离的行动Nef协同有效地保护细胞免受HIV重叠感染的水平上的融合的病毒包膜与plasma membrane.Conclusions：HIV已经发展了两个独立的活动Nef下调受体复合物，并促进其有效的复制和传播。这种逃避策略可能代表了致病因子Nef在体内提高病毒复制从而促进AIDS发病的机制。
Background: Viruses frequently render cells refractory to subsequent infection with the same virus. This state of superinfection immunity counteracts potentially detrimental consequences for the infected cell and facilitates high-level replication and viral spread in the host.Results: Here, we show that human immunodeficiency virus (HIV) employs its early gene product Nef to efficiently interfere with superinfection at the viral-entry step. In this context, we identify the downregulation of cell-surface CCR5, the major HIV coreceptor, as a novel and highly conserved activity of Nef. Nef targets the CCR5 coreceptor and the HIV binding receptor CD4 via distinct cellular machineries to enhance the endocytosis rate of both HIV receptor components and to accelerate their degradation. Functionally, these genetically separable actions by Nef synergized to efficiently protect cells from HIV superinfection at the level of fusion of the viral envelope with the plasma membrane.Conclusions: HIV has evolved two independent activities for Nef to downregulate the receptor complex and to facilitate its efficient replication and spread. This evasion strategy likely represents a mechanism by which the pathogenicity factor Nef elevates viral replication in vivo and thus promotes AIDS pathogenesis.