Vpx and Vpr proteins of HIV-2 up-regulate the viral infectivity by a distinct mechanism in lymphocytic cells
Vpx and Vpr proteins of HIV-2 up-regulate the viral infectivity by a distinct mechanism in lymphocytic cells
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DOI：
10.1016/s1286-4579(03)00042-x
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发表时间：
2003-04-01
影响因子：
5.8
通讯作者：
Fujita, M
中科院分区：
文献类型：
--
作者：
Ueno, F;Shiota, H;Fujita, M
在新建立的淋巴细胞系HSC-F中，监测携带Vpx、Vpr和两个基因移码突变的人类免疫缺陷病毒2型（HIV-2）突变体的生长潜力。值得注意的是，在这些细胞中，vpx单突变体的复制受到严重损害，而vpr没有，而vpx-vpr双突变体的复制受到更大的损害。Vpx单突变体和Vpx-Vpr双突变体的复制缺陷位点被证明分别映射到病毒基因组的核输入，以及该过程和病毒组装/释放阶段。虽然vpr的突变效应很小，但vpx突变体相对于野生型病毒在一个循环中的复制效率估计为10%。hpx、vpr和hpx-vpr突变病毒在HSC-F细胞中的生长表型基本上在原代人淋巴细胞中重复。在原代人巨噬细胞中，vpx和vpx-vpr突变体根本不生长，而vpr突变体的生长与野生型病毒一样。这些结果强烈表明，Vpx是至关重要的上调HIV-2的复制在天然靶细胞中，通过增强基因组核输入，Vpr促进HIV-2的复制有点，至少在淋巴细胞，在一个非常晚的复制阶段。(C)2003年，Elsevier SAS科学与医学版。All rights reserved.
Mutants of human immunodeficiency virus type 2 (HIV-2) carrying a frame-shift mutation in vpx, vpr, and in both genes were monitored for their growth potentials in a newly established lymphocytic cell line, HSC-F. Worthy of note, the replication of a vpx single mutant, but not vpr, was severely impaired in these cells, and that of a vpx-vpr double mutant was more damaged. Defective replication sites of the vpx single and vpx-vpr double mutants were demonstrated to be mapped, respectively, to the nuclear import of viral genome, and to both, this process and the virus assembly/release stage. While the mutational effect of vpr was small, the replication efficiency in one cycle of the vpx mutant relative to that of wild-type virus was estimated to be 10%. The growth phenotypes of the vpx, vpr, and vpx-vpr mutant viruses in HSC-F cells were essentially repeated in primary human lymphocytes. In primary human macrophages, whereas the vpx and vpx-vpr mutants did not grow at all, the vpr mutant grew equally as well as the wild-type virus. These results strongly suggested that Vpx is critical for up-regulation of HIV-2 replication in natural target cells by enhancing the genome nuclear import, and that Vpr promotes HIV-2 replication somewhat, at least in lymphocytic cells, at a very late replication phase. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.