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马传染性贫血病毒在马基因组中的整合特征

Characterization of Equine Infectious Anemia Virus Integration in the Horse Genome.

作者信息

Liu Qiang, Wang Xue-Feng, Ma Jian, He Xi-Jun, Wang Xiao-Jun, Zhou Jian-Hua

机构信息

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, China.

出版信息

Viruses. 2015 Jun 19;7(6):3241-60. doi: 10.3390/v7062769.

Abstract

Human immunodeficiency virus (HIV)-1 has a unique integration profile in the human genome relative to murine and avian retroviruses. Equine infectious anemia virus (EIAV) is another well-studied lentivirus that can also be used as a promising retro-transfection vector, but its integration into its native host has not been characterized. In this study, we mapped 477 integration sites of the EIAV strain EIAVFDDV13 in fetal equine dermal (FED) cells during in vitro infection. Published integration sites of EIAV and HIV-1 in the human genome were also analyzed as references. Our results demonstrated that EIAVFDDV13 tended to integrate into genes and AT-rich regions, and it avoided integrating into transcription start sites (TSS), which is consistent with EIAV and HIV-1 integration in the human genome. Notably, the integration of EIAVFDDV13 favored long interspersed elements (LINEs) and DNA transposons in the horse genome, whereas the integration of HIV-1 favored short interspersed elements (SINEs) in the human genome. The chromosomal environment near LINEs or DNA transposons potentially influences viral transcription and may be related to the unique EIAV latency states in equids. The data on EIAV integration in its natural host will facilitate studies on lentiviral infection and lentivirus-based therapeutic vectors.

摘要

与鼠类和禽类逆转录病毒相比,人类免疫缺陷病毒1型(HIV-1)在人类基因组中具有独特的整合模式。马传染性贫血病毒(EIAV)是另一种经过充分研究的慢病毒,也可作为一种有前景的逆转录转染载体,但尚未对其在天然宿主中的整合情况进行表征。在本研究中,我们绘制了体外感染期间EIAV毒株EIAVFDDV13在马胎儿皮肤(FED)细胞中的477个整合位点。还分析了已发表的EIAV和HIV-1在人类基因组中的整合位点作为参考。我们的结果表明,EIAVFDDV13倾向于整合到基因和富含AT的区域,并避免整合到转录起始位点(TSS),这与EIAV和HIV-1在人类基因组中的整合情况一致。值得注意的是,EIAVFDDV13的整合在马基因组中有利于长散在元件(LINEs)和DNA转座子,而HIV-1的整合在人类基因组中有利于短散在元件(SINEs)。LINEs或DNA转座子附近的染色体环境可能影响病毒转录,并且可能与马科动物中独特的EIAV潜伏状态有关。EIAV在其天然宿主中的整合数据将有助于慢病毒感染和基于慢病毒的治疗载体的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97a8/4488736/22c92284c4a4/viruses-07-02769-g001.jpg

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