HIV-1 viral protein R (Vpr) regulates viral replication and cellular proliferation in T cells and monocytoid cells in vitro
HIV-1 viral protein R (Vpr) regulates viral replication and cellular proliferation in T cells and monocytoid cells in vitro
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DOI：
10.1002/jlb.62.1.93
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发表时间：
1997-07-01
影响因子：
5.5
通讯作者：
Weiner, DB
中科院分区：
文献类型：
--
作者：
Ayyavoo, V;Mahalingam, S;Weiner, DB
在HIV-1的可能的辅助基因中，96个氨基酸的病毒粒子相关的VPR基因产物被描述为具有一些新的生物活性，包括胞浆到核的易位，使HIV能够在不分裂的细胞中感染和复制，并增加病毒的复制，特别是在巨噬细胞中。独自一人；有了这些病毒效应，我们发现HIV-1VPR在HIV感染的靶细胞中诱导了戏剧性的生物学变化，包括诱导转录模式、形态变化和完全抑制增殖，这些变化统称为分化，这些变化发生在没有其他病毒基因产物的情况下，表明VPR部分或可能仅通过调节靶细胞的状态而不是直接作用于病毒来介导其前病毒效应。T细胞系的增殖抑制已被几个组延长，以证明抑制增殖是通过G2细胞周期停滞，进一步支持了VPR直接作用于细胞靶点的观点。我们最近描述了vpr在调节糖皮质激素途径中的作用，vpr参与了细胞状态的调节、胞浆到胞核的易位以及宿主细胞转录的调节。值得注意的是，某些抗糖皮质激素化合物在体外调节vpr的活性，这些结果支持宿主细胞含有vpr介导其活性的特定受体分子(S)的观点，因此vpr是抗艾滋病毒药物开发的独特靶点，对HIV-1疾病的进展具有重要意义。
Among the putative accessory genes of HIV-1, the 96-amino-acid virion-associated vpr gene product has been described to have several novel biological activities, These include cytoplasmic-to-nuclear translocation, which empowers HIV to infect and replicate in non-dividing cells and to increase viral replication, particularly in macrophages. Alone; with these viral effects, we found that HIV-1 Vpr induces dramatic biological changes in the target cells of HIV infection, including induction of changes in transcriptional patterns, morphological changes, and complete inhibition of proliferation, which collectively was termed differentiation, These changes occur in the absence of other viral gene products, suggesting that Vpr mediates its proviral effects partially or perhaps solely through modulation of the state of the target cell rather than directly on the virus, The inhibition of proliferation in T cell lines has been extended by several groups to demonstrate that the inhibition of proliferation is through G2 cell cycle arrest, further supporting the idea that Vpr acts directly on cellular targets, We have recently described a role for Vpr in modulating the glucocorticoid pathway, which is involved in the regulation of the state of the cell, in cytoplasmic-to-nuclear translocation, and in modulation of host cell transcription, It is important to note that certain antiglucocorticoid compounds modulate Vpr activity in vitro, These results support the idea that the host cell contains specific receptor molecule(s) through which Vpr mediates its activity, Consequently, Vpr represents a unique-target for anti-HIV drug development and has significance for HIV-1 disease progression.