Discovery and analysis of the first endogenous lentivirus

Discovery and analysis of the first endogenous lentivirus
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DOI:
10.1073/pnas.0700471104
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发表时间:
2007-04-10
影响因子:
11.1
通讯作者:
Gifford, Robert J.
Gifford, Robert J.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Katzourakis, Aris;Tristem, Michael;Gifford, Robert J.

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慢病毒与哺乳动物的多种慢性疾病有关。这些疾病包括免疫缺陷(如人类的HIV/AlDS)、恶性肿瘤以及灵长类动物、猫科动物和各种野生和家养有蹄类动物的淋巴和神经系统疾病。对现代慢病毒基因组序列的进化分析表明,它们出现的时间相对较晚,但未能确定任何同源的垂直传播的例子,这意味着它们的长期进化历史和起源仍然未知。在这里,我们报告的发现和表征的逆转录病毒序列属于一个新的慢病毒亚组从欧洲兔(Oryctolagus cuniculus)。这些病毒是描述的第一个同源的例子,有超过700万年的历史,因此为慢病毒的古老起源提供了第一个证据。尽管是古老的,这个亚群包含了许多在今天的慢病毒中发现的特征,例如tat和rev基因的存在,因此也表明了慢病毒基因表达复杂调控的古老起源。虽然我们描述的病毒是有缺陷的,但重建感染性祖细胞可以为慢病毒生物学和宿主相互作用提供新的见解。
The lentiviruses are associated with a wide range of chronic diseases in mammals. These include immunodeficiencies (such as HIV/AlDS in humans), malignancies, and lymphatic and neurological disorders in primates, felids, and a variety of wild and domesticated ungulates. Evolutionary analyses of the genomic sequences of modern-day lentiviruses have suggested a relatively recent date for their emergence, but the failure to identify any enclogenous, vertically transmitted examples has meant that their longer term evolutionary history and origin remain unknown. Here we report the discovery and characterization of retroviral sequences belonging to a new lentiviral subgroup from the European rabbit (Oryctolagus cuniculus). These viruses, the first enclogenous examples described, are > 7 million years old and thus provide the first evidence for an ancient origin of the lentiviruses. Despite being ancient, this subgroup contains many of the features found in present-day lentiviruses, such asthe presenceof tatand revgenes, thusalso indicating an ancientorigin forthe complex regulation of lentivirus gene expression. Although the virus we describe is defective, reconstruction of an infectious progenitor could provide novel insights into lentivirus biology and host interactions.