The conserved core of human immunodeficiency virus type 1 Nef is essential for association with Lck and for enhanced viral replication in T-lymphocytes
The conserved core of human immunodeficiency virus type 1 Nef is essential for association with Lck and for enhanced viral replication in T-lymphocytes
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DOI：
10.1006/viro.1999.9937
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发表时间：
1999-11-10
期刊：
影响因子：
3.7
通讯作者：
Parks, WP
中科院分区：
文献类型：
--
作者：
Cheng, H;Hoxie, J;Parks, WP
包括人类免疫缺陷病毒1型（HIV-1）和猿猴免疫缺陷病毒（SIV）的灵长类慢病毒的Nei蛋白是与增加的病毒复制和增强的致病性相关的肉豆蔻酰化蛋白。Nef增强T淋巴细胞活化和增强HIV-1衣壳的丝氨酸磷酸化与病毒复制增加相关。我们报告的Nei蛋白与Src激酶的功能相互作用。来自HIV-1和SIV的Nei蛋白与Lck以及Hck、林恩和Fyn结合。Lck的SH 3和SH 2结构域足以与非酪氨酸磷酸化的Ne共沉淀？proteins. HIV-1 Nef的保守核心区对于与Lck的相互作用是必需的，并且对于增强HIV-1在T淋巴细胞中的复制也是重要的。此外，我们发现：SIV和HIV-1 Nef蛋白的酪氨酸磷酸化差异。激酶活性Lck酪氨酸磷酸化SIVmac 239 Nei，但不磷酸化HIV-1 Nei。这些数据表明，Nei和Lck的关联是增强HIV-1和SIV在T淋巴细胞中的病毒复制的核心。(C)北京：科学出版社.
The Nei protein of the primate lentiviruses, including human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV), is a myristylated protein associated with increased viral replication and enhanced pathogenicity. Both the potentiation of T-lymphocyte activation and the enhanced serine-phosphorylation of HIV-1 capsid by Nef correlate with increased viral replication. We report the functional interactions of the Nei proteins with Src kinases. The Nei proteins from HIV-1 and SIV bind to Lck as well as Hck, Lyn, and Fyn. The SH3 and SH2 domains of Lck are sufficient for coprecipitation with non-tyrosine-phosphorylated Ne? proteins. The conserved core region of HIV-1 Nef is essential for the interaction with Lck and is also important for enhanced HIV-1 replication in T-lymphocytes. In addition, we show that: SIV and HIV-1 Nef proteins are differentially tyrosine-phosphorylated. The kinase-active Lck tyrosine-phosphorylates SIVmac239 Nei but does not phosphorylate HIV-1 Nei. These data suggest that the association of Nei and Lck is central to the enhanced viral replication of HIV-1 and SIV in T-lymphocytes. (C) 1999 Academic Press.