A human nuclear shuttling protein that interacts with human immunodeficiency virus type 1 matrix is packaged into virions
A human nuclear shuttling protein that interacts with human immunodeficiency virus type 1 matrix is packaged into virions
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DOI：
10.1128/jvi.74.24.11811-11824.2000
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发表时间：
2000-12-01
影响因子：
5.4
通讯作者：
Boeke, JD
中科院分区：
文献类型：
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作者：
Gupta, K;Ott, D;Boeke, JD
人类免疫缺陷病毒1型（HIV-1）整合前复合物（PIG）的主动核输入对于非分裂细胞的生产性感染至关重要。PIC的核输入由HIV-1基质蛋白介导，其在病毒进入期间以及可能在促进Pr 55（Gag）和基因组RNA输出的病毒体产生期间也起几个关键作用。使用酵母双杂交筛选，我们确定了一种新的人类病毒体相关的基质相互作用蛋白（货车），在脊椎动物中高度保守，并在大多数人类组织中表达。其表达在CD 4（+）T细胞活化后上调。货车被有效地整合到HIV-1病毒体中，并且像基质一样在细胞核和细胞质之间穿梭。此外，货车的过表达显著抑制组织培养中的HIV-1复制。我们建议，货车调节基质核定位，并通过扩展，在病毒粒子生产过程中，PIC的核进口和Pr 55（Gag）和病毒基因组RNA的出口。我们的数据表明，这种调节机制反映了一个更全球性的核质转运的调节过程。
Active nuclear import of the human immunodeficiency virus type 1 (HIV-1) preintegration complex (PIG) is essential for the productive infection of nondividing cells. Nuclear import of the PIC is mediated by the HIV-1 matrix protein, which also plays several critical roles during viral entry and possibly during virion production facilitating the export of Pr55(Gag) and genomic RNA. Using a yeast two-hybrid screen, we identified a novel human virion-associated matrix-interacting protein (VAN) that is highly conserved in vertebrates and expressed in most human tissues. Its expression is upregulated upon activation of CD4(+) T cells. VAN is efficiently incorporated into HIV-1 virions and, like matrix, shuttles between the nucleus and cytoplasm. Furthermore, overexpression of VAN significantly inhibits HIV-1 replication in tissue culture. We propose that VAN regulates matrix nuclear localization and, by extension, both nuclear import of the PIC and export of Pr55(Gag) and viral genomic RNA during virion production. Our data suggest that this regulatory mechanism reflects a more global process for regulation of nucleocytoplasmic transport.