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首页> 外文期刊>AIDS Research and Human Retroviruses >A genomic and bioinformatics analysis of the integration of HIV in peripheral blood mononuclear cells.
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A genomic and bioinformatics analysis of the integration of HIV in peripheral blood mononuclear cells.

机译：对HIV在外周血单核细胞中整合的基因组学和生物信息学分析。

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摘要

The mechanistic basis of the target-site preference of lentivirus DNA integration is not well understood. In the present in silico study, we describe the integrational profile of simultaneous HIV-1 and HIV-2 infection. A total of 352 genomic DNA sequences from human peripheral blood mononuclear cells (PBMCs) obtained from GenBank and possessing the 5' LTR of HIV were used to characterize the structure and composition of local chromatin associated with high frequency integration sites. These sequences were aligned with the draft human genome (hg18) using BLAST (NCBI) and BLAT (UCSC) in order to derive information about chromosome localization, functional aspects of coding protein genes, CpG island number, and repetitive elements flanking integration sites. No significant differences in the integrational profile between HIV-1 and HIV-2 were found. However, we observed a tendency in both lentiviruses to integrate in the vicinity of protein coding genes. Multiple regression analysis showed a strong correlation between the number of genes and the number of CpG islands in regions with high integration frequency, mainly in chromosome 17 (R = 0.95, p < 0.05). Our results provide strong evidence that HIV-1 and HIV-2 have common genomic environments in the local chromatin regions with high gene density and CpG islands. The understanding of local genomic environments with a high frequency of integration would be the starting point to develop novel antiviral strategies for lentiviral infection.
机译：慢病毒DNA整合的目标位点偏好的机制基础尚不清楚。在目前的计算机研究中，我们描述了同时感染HIV-1和HIV-2的整合情况。从GenBank获得并具有HIV 5'LTR的人类外周血单核细胞（PBMC）的总共352个基因组DNA序列用于表征与高频整合位点相关的局部染色质的结构和组成。使用BLAST（NCBI）和BLAT（UCSC）将这些序列与人类基因组草图（hg18）进行比对，以便获得有关染色体定位，编码蛋白基因的功能方面，CpG岛数和侧翼整合位点的重复信息。在HIV-1和HIV-2之间的整合情况中未发现显着差异。但是，我们观察到两种慢病毒在蛋白质编码基因附近整合的趋势。多元回归分析显示，在整合频率较高的区域，主要在第17号染色​​体上，基因数量与CpG岛数量之间存在很强的相关性（R = 0.95，p <0.05）。我们的结果提供了有力的证据，证明HIV-1和HIV-2在具有高基因密度和CpG岛的局部染色质区域具有共同的基因组环境。对本地基因组环境的高频率整合的了解将是开发针对慢病毒感染的新型抗病毒策略的起点。

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