Integration targeting by avian sarcoma-leukosis virus and human immunodeficiency virus in the chicken genome
Integration targeting by avian sarcoma-leukosis virus and human immunodeficiency virus in the chicken genome
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DOI：
10.1128/jvi.79.18.12035-12044.2005
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发表时间：
2005-09-01
影响因子：
5.4
通讯作者：
Bushman, FD
中科院分区：
文献类型：
--
作者：
Barr, SD;Leipzig, J;Bushman, FD
我们分析了禽肉瘤白血病病毒（ASLV）和人类免疫缺陷病毒（HIV）DNA的整合位点在鸡基因组序列草案中的位置，目的是评估物种特异性对整合的影响，并与鸡内源性逆转录病毒（ERVs）的分布进行比较。我们用ASLV或HIV感染鸡胚成纤维细胞（CEF），并对宿主和病毒DNA之间的863个连接点进行测序。通过未感染或ASLV感染的CEF细胞的转录谱分析与细胞基因活性的关系。ASLV弱地倾向于整合在活性转录单位（TU）中，而HIV强烈地倾向于活性TU，这是先前在人类细胞中观察到的整合趋势。相反，ERV主要在TU外积累，包括与ASLV相关的ERV。TU内存在的少数ERV主要处于反义方向;因此，病毒剪接和多腺苷酸化信号不会破坏细胞mRNA合成。相比之下，TU内的从头ASLV整合位点未显示取向偏倚。比较从头ASLV整合位点与ERV的分布表明，针对基因破坏的纯化选择，而不是初始整合靶向，可能决定了ERV的分布。进一步的分析表明，ERV在人类，小鼠和大鼠中显示出相似的分布，这表明纯化选择也决定了它们的分布。
We have analyzed the placement of sites of integration of avian sarcoma-leukosis virus (ASLV) and human immunodeficiency virus (HIV) DNA in the draft chicken genome sequence, with the goals of assessing species-specific effects on integration and allowing comparison to the distribution of chicken endogenous retroviruses (ERVs). We infected chicken embryo fibroblasts (CEF) with ASLV or HIV and sequenced 863 junctions between host and viral DNA. The relationship with cellular gene activity was analyzed by transcriptional profiling of uninfected or ASLV-infected CEF cells. ASLV weakly favored integration in active transcription units (TUs), and HIV strongly favored active TUs, trends seen previously for integration in human cells. The ERVs, in contrast, accumulated mostly outside TUs, including ERVs related to ASLV. The minority of ERVs present within TUs were mainly in the antisense orientation; consequently, the viral splicing and polyadenylation signals would not disrupt cellular mRNA synthesis. In contrast, de novo ASLV integration sites within TUs showed no orientation bias. Comparing the distribution of de novo ASLV integration sites to ERVs indicated that purifying selection against gene disruption, and not initial integration targeting, probably determined the ERV distribution. Further analysis indicated that ERVs in humans, mice, and rats showed similar distributions, suggesting purifying selection dictated their distributions as well.