HIV-1 NEF LEADS TO INHIBITION OR ACTIVATION OF T-CELLS DEPENDING ON ITS INTRACELLULAR-LOCALIZATION
HIV-1 NEF LEADS TO INHIBITION OR ACTIVATION OF T-CELLS DEPENDING ON ITS INTRACELLULAR-LOCALIZATION
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DOI：
10.1016/1074-7613(94)90068-x
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发表时间：
1994-08-01
期刊：
影响因子：
32.4
通讯作者：
PETERLIN, BM
中科院分区：
文献类型：
--
作者：
BAUR, AS;SAWAI, ET;PETERLIN, BM
灵长类慢病毒的Nef是猴病毒血症和进展为AIDS所必需的。Nef对细胞中病毒复制的影响也有阴性、阳性和无影响的报道。为了调和这些观察结果，我们在Jurkat细胞中表达了杂交CD 8-Nef蛋白。发现两种相反的表型，这取决于Nef的细胞内定位。表达在细胞质或细胞表面上，嵌合体抑制或激活来自T细胞抗原受体的早期信号事件。活化的Jurkat细胞因凋亡而死亡，只有表达截短Nefs的突变nef基因的细胞存活，这使得Nef无功能。这些突变与体外传代的其他病毒株中的突变相同。Nef的这些位置效应不仅协调了Nef的不同表型，并表明其N-末端肉豆蔻基化的作用，而且还解释了Nef在HIV感染和进展为AIDS中的作用。
Nef of primate lentiviruses is required for viremia and progression to AIDS in monkeys. Negative, positive, and no effects of Nef have also been reported on viral replication in cells. To reconcile these observations, we expressed a hybrid CD8-Nef protein in Jurkat cells. Two opposite phenotypes were found, which depended on the intracellular localization of Nef. Expressed in the cytoplasm or on the cell surface, the chimera inhibited or activated early signaling events from the T cell antigen receptor. Activated Jurkat cells died by apoptosis, and only cells with mutated nef genes expressing truncated Nefs survived, which rendered Nef nonfunctional. These mutations paralleled those in other viral strains passaged in vitro. Not only do these positional effects of Nef reconcile diverse phenotypes of Nef and suggest a role for its N-terminal myristylation, but they also explain effects of Nef in HIV infection and progression to AIDS.