HIV-1 Nef association with cellular serine kinase correlates with enhanced virion infectivity and efficient proviral DNA synthesis.
HIV-1 Nef association with cellular serine kinase correlates with enhanced virion infectivity and efficient proviral DNA synthesis.
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HIV-1 Nef 与细胞丝氨酸激酶的关联与增强的病毒粒子感染性和有效的前病毒 DNA 合成相关。
DOI：
10.1006/viro.1996.0531
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发表时间：
1996
期刊：
影响因子：
3.7
通讯作者：
Cheng-Mayer,C
中科院分区：
文献类型：
--
作者：
Wiskerchen,M;Cheng-Mayer,C
我们先前报道了Nef与细胞丝氨酸激酶（E. T. Sawai等人，Proc. Natl. Acad. Sci. USA91，1539-1543，1994）。在本研究中，我们进一步定义了Nef序列的要求，这种激酶协会和调查的影响，这种激酶协会对HIV-1 Nef的功能。我们观察到，除了膜靶向信号和核心区域内的保守arg-arg残基，Nef的富含脯氨酸的结构域中的突变也影响其与丝氨酸激酶活性相关的能力。包含Nef的arg-arg残基的区域显示对于Nef介导的细胞表面CD 4下调以及病毒生长特性的增强是重要的。这类似于先前对于Nef的N-末端处的膜靶向位点所观察到的。相反，Nef的富含脯氨酸的区域被发现参与介导有效的前病毒DNA合成和增强的病毒体感染功能，但对于Nef下调CD 4不是必需的。因此，似乎Nef的丝氨酸激酶缔合对于有效的前病毒DNA合成和促进Nef+病毒的病毒体感染性是必需的，但对于Nef下调CD 4受体是不必要的。这些研究结果定义了Nef的三个功能域，它们是与丝氨酸激酶活性相互作用所必需的，并表明通过肉豆蔻酰化和Nef的arg-arg区域的细胞相互作用事件位于通过富含脯氨酸的结构域的相互作用事件的上游。
We previously reported on the association of Nef with a cellular serine kinase (E. T. Sawaiet al., Proc. Natl. Acad. Sci. USA91, 1539–1543, 1994). In the present study, we further define the Nef sequence requirements for this kinase association and investigate the effect of this kinase association on functions of HIV-1 Nef. We observe that, in addition to the membrane targeting signal and the conserved arg–arg residues within the core region, mutations in the proline-rich domain of Nef also affect its ability to associate with the serine kinase activity. The region encompassing the arg–arg residues of Nef is shown to be important for Nef-mediated cell-surface CD4 down-modulation as well as enhancement of viral growth properties. This is similar to what has previously been observed for the membrane targeting site at the N-terminus of Nef. In contrast, the proline-rich region of Nef is found to be involved in mediating efficient proviral DNA synthesis and the enhanced virion-infectivity function, but is not necessary for CD4 down-modulation by Nef. Thus, it appears that serine kinase association of Nef is necessary for efficient proviral DNA synthesis and for promotion of virion infectivity of Nef+viruses, but is dispensable for down-regulation of the CD4 receptor by Nef. These findings define three functional domains of Nef that are required for its interaction with the serine kinase activity and suggest that the cellular interaction events via the myristoylation and arg–arg regions of Nef lie upstream of the interaction event via the proline-rich domain.