HIV-1 accessory protein Vpr: relevance in the pathogenesis of HIV and potential for therapeutic intervention.

HIV-1 accessory protein Vpr: relevance in the pathogenesis of HIV and potential for therapeutic intervention.
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DOI:
10.1186/1742-4690-8-25
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发表时间:
2011-04-13
期刊:
影响因子:
3.3
通讯作者:
Rappaport J
Rappaport J
中科院分区:
医学2区
文献类型:
--
作者:
Kogan M;Rappaport J

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HIV蛋白Vpr是一种多功能辅助蛋白,对于靶CD 4 + T细胞和巨噬细胞的有效病毒感染至关重要。Vpr被整合到病毒体中,并起到将整合前复合物转运到细胞核中的作用,在细胞核中完成病毒整合到宿主基因组中的过程。这种作用在巨噬细胞中特别重要,由于它们的终末分化和非增殖状态,否则对HIV感染更难治。Vpr具有几种其他关键功能,包括激活HIV-1 LTR转录、由于DCAF-1结合导致的细胞周期停滞以及直接和间接促进T细胞功能障碍。另一方面,在巨噬细胞中Vpr与分子途径的相互作用支持HIV感染在髓系细胞中的持续储存库的积累。Vpr在病毒生命周期中的作用以及其对免疫细胞的影响似乎在AIDS的免疫发病机制和HIV诱导的终末器官疾病的发展中起重要作用。鉴于Vpr在病毒感染、复制和感染持续中的关键功能,该蛋白代表了治疗干预的有吸引力的靶标。
The HIV protein, Vpr, is a multifunctional accessory protein critical for efficient viral infection of target CD4+ T cells and macrophages. Vpr is incorporated into virions and functions to transport the preintegration complex into the nucleus where the process of viral integration into the host genome is completed. This action is particularly important in macrophages, which as a result of their terminal differentiation and non-proliferative status, would be otherwise more refractory to HIV infection. Vpr has several other critical functions including activation of HIV-1 LTR transcription, cell-cycle arrest due to DCAF-1 binding, and both direct and indirect contributions to T-cell dysfunction. The interactions of Vpr with molecular pathways in the context of macrophages, on the other hand, support accumulation of a persistent reservoir of HIV infection in cells of the myeloid lineage. The role of Vpr in the virus life cycle, as well as its effects on immune cells, appears to play an important role in the immune pathogenesis of AIDS and the development of HIV induced end-organ disease. In view of the pivotal functions of Vpr in virus infection, replication, and persistence of infection, this protein represents an attractive target for therapeutic intervention.
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发表时间: 2008-07-18
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