Vpx is critical for reverse transcription of the human immunodeficiency virus type 2 genome in macrophages

Vpx is critical for reverse transcription of the human immunodeficiency virus type 2 genome in macrophages
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DOI:
10.1128/jvi.01003-07
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发表时间:
2008-08-01
影响因子:
5.4
通讯作者:
Adachi, Akio
Adachi, Akio
中科院分区:
医学2区
文献类型:
--
作者:
Fujita, Mikako;Otsuka, Masami;Adachi, Akio

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比较和定量评价了野生型和vpx缺陷型人类免疫缺陷病毒2型(HIV-2)克隆在人单核细胞衍生的巨噬细胞(MDM)和淋巴细胞中合成病毒DNA的能力。虽然vpx缺陷型突变体直接合成的病毒DNA的野生型病毒和正常的淋巴细胞,没有明显的病毒DNA被检测到的突变体感染的MDM。为了证实这一发现,并确定是否有一些特定的区域(S)Vpx的病毒DNA合成的MDM中至关重要的,我们产生了一系列的Vpx位点特异性点突变体,并检查其表型。得到的五个突变体,没有感染性的MDM,显示,无一例外地,同样的缺陷作为vpx缺陷型突变体。我们的结果清楚地表明,整个Vpx蛋白是人类MDM中HIV-2基因组逆转录的关键。
The abilities of wild-type and vpx-defective human immunodeficiency virus type 2 (HIV-2) clones to synthesize viral DNA in human monocyte-derived macrophages (MDMs) and lymphocytic cells were comparatively and quantitatively evaluated. While the vpx-defective mutant directed the synthesis of viral DNA comparably to the wild-type virus and normally in lymphocytic cells, no appreciable viral DNA was detected in MDMs infected with the mutant. To substantiate this finding and to determine whether there is some specific region(s) in Vpx crucial for viral DNA synthesis in MDMs, we generated a series of site-specific point mutants of vpx and examined their phenotypes. The resultant five mutants, with no infectivity for MDMs, showed, without exception, the same defect as the vpx-defective mutant. Our results here clearly demonstrated that the entire Vpx protein is critical for reverse transcription of the HIV-2 genome in human MDMs.