The integration of a macrophage-adapted live vaccine strain of equine infectious anaemia virus (EIAV) in the horse genome

文献类型： 外文期刊

第一作者： Liu, Qiang

作者： Liu, Qiang;Wang, Xue-Feng;Du, Cheng;Lin, Yue-Zhi;Ma, Jian;Zhou, Jian-Hua;Wang, Xiaojun;Wang, Yu-Hong

作者机构：

关键词： lentivirus;EIAV;macrophages;integration sites;RefSeq genes;LINEs

期刊名称：JOURNAL OF GENERAL VIROLOGY （ 影响因子：3.891； 五年影响因子：3.719 ）

ISSN： 0022-1317

年卷期： 2017 年 98 卷 10 期

页码：

收录情况： SCI

摘要： Integration is an important feature of retroviruses and retrovirus-based therapeutic transfection vectors. The non-primate lentivirus equine infectious anaemia virus (EIAV) primarily targets macrophages/monocytes in vivo. Investigation of the integration features of EIAV(DLV121) strains, which are adapted to donkey monocyte-derived macrophages (MDMs), is of great interest. In this study, we analysed the integration features of EIAV(DLV121) in equine MDMs during in vitro infection. Our previously published integration sites (IS) for EIAV(FDDV13) in fetal equine dermal (FED) cells were also analysed in parallel as references. Sequencing of the host genomic regions flanking the viral IS showed that reference sequence (RefSeq) genes were preferentially targeted for integration by EIAV(DLV121). Introns, AT-rich regions, long interspersed nuclear elements (LINEs) and DNA transposons were also predominantly biased toward viral insertion, which is consistent with EIAV(FDDV13) integration into the horse genome in FED cells. In addition, the most significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, specifically gag junctions for EIAV(DLV121) and tight junctions for EIAV(FDDV13), are regulators of metabolic function, which is consistent with the common bioprocesses, specifically cell cycle and chromosome/DNA organization, identified by gene ontology (GO) analysis. Our results demonstrate that EIAV integration occurs in regions that harbour structural and topological features of local chromatin in both macrophages and fibroblasts. Our data on EIAV will facilitate further understanding of lentivirus infection and the development of safer and more effective gene therapy vectors.

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