内源性猫白血病病毒长末端重复整合位点多样性在有亲缘关系和无亲缘关系的家猫中变化很大。

IF 2.7 3区 医学 Q3 VIROLOGY Retrovirology Pub Date : 2024-02-12 DOI:10.1186/s12977-024-00635-0
Elliott S Chiu, Coby A McDonald, Roderick B Gagne, Henry Dunkleberger, Matthew Moxcey, Sue VandeWoude
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引用次数: 0

摘要

内源性逆转录病毒(ERV)是脊椎动物进化史的指标,作为同源调节因子发挥着重要作用。ERV长末端重复(LTR)元件可作为顺式激活启动子或反式激活增强子元件,改变远离LTR插入位点的基因转录。我们以前曾发现,个体猫体内的内源性猫白血病病毒(FeLV)-LTR拷贝数变异与对毒性 FeLV 疾病的易感性成反比。为了评估 FeLV-LTR 插入特征,我们使用诱饵连接子介导的 PCR 方法评估了来自三个不同基因种群的 20 只猫的 enFeLV-LTR 整合位点多样性。我们记录了 765 个整合位点,这些位点在个体间的分布不均。只有三个 LTR 整合位点为所有个体所共有,而 412 个位点为单个个体所独有。当原代成纤维细胞受到外源 FeLV 挑战时,我们发现外源和内源 FeLV 同源物的表达均显著增加,这支持了之前关于外源 FeLV-enFeLV 潜在相互作用的发现;然而,病毒挑战并未引起与绝大多数整合位点相关基因的转录变化。本研究评估了动物个体的 FeLV-LTR 整合位点,提供了独特的转座子基因型。此外,我们还记录了 LTR 整合位点位置的巨大个体差异,即使在高度近交的种群中也是如此,并为了解内源性逆转录病毒元件位置对宿主基因转录的潜在影响提供了一个框架。
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Endogenous feline leukemia virus long terminal repeat integration site diversity is highly variable in related and unrelated domestic cats.

Endogenous retroviruses (ERV) are indicators of vertebrate evolutionary history and play important roles as homeostatic regulators. ERV long terminal repeat (LTR) elements may act as cis-activating promoters or trans-activating enhancer elements modifying gene transcription distant from LTR insertion sites. We previously documented that endogenous feline leukemia virus (FeLV)-LTR copy number variation in individual cats tracks inversely with susceptibility to virulent FeLV disease. To evaluate FeLV-LTR insertion characteristics, we assessed enFeLV-LTR integration site diversity in 20 cats from three genetically distinct populations using a baited linker-mediated PCR approach. We documented 765 individual integration sites unequally represented among individuals. Only three LTR integration sites were shared among all individuals, while 412 sites were unique to a single individual. When primary fibroblast cultures were challenged with exogenous FeLV, we found significantly increased expression of both exogenous and endogenous FeLV orthologs, supporting previous findings of potential exFeLV-enFeLV interactions; however, viral challenge did not elicit transcriptional changes in genes associated with the vast majority of integration sites. This study assesses FeLV-LTR integration sites in individual animals, providing unique transposome genotypes. Further, we document substantial individual variation in LTR integration site locations, even in a highly inbred population, and provide a framework for understanding potential endogenous retroviral element position influence on host gene transcription.

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来源期刊
Retrovirology
Retrovirology 医学-病毒学
CiteScore
5.80
自引率
3.00%
发文量
24
审稿时长
>0 weeks
期刊介绍: Retrovirology is an open access, online journal that publishes stringently peer-reviewed, high-impact articles on host-pathogen interactions, fundamental mechanisms of replication, immune defenses, animal models, and clinical science relating to retroviruses. Retroviruses are pleiotropically found in animals. Well-described examples include avian, murine and primate retroviruses. Two human retroviruses are especially important pathogens. These are the human immunodeficiency virus, HIV, and the human T-cell leukemia virus, HTLV. HIV causes AIDS while HTLV-1 is the etiological agent for adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. Retrovirology aims to cover comprehensively all aspects of human and animal retrovirus research.
期刊最新文献
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