Parallel germline infiltration of a lentivirus in two Malagasy lemurs.
Parallel germline infiltration of a lentivirus in two Malagasy lemurs.
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DOI：
10.1371/journal.pgen.1000425
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发表时间：
2009-03
期刊：
影响因子：
4.5
通讯作者：
Feschotte C
中科院分区：
文献类型：
--
作者：
Gilbert C;Maxfield DG;Goodman SM;Feschotte C
逆转录病毒通常感染宿主的体细胞，并水平传播，即以外源方式传播。然而，有时，一些逆转录病毒也可以感染并整合到生殖细胞的基因组中，这可能允许它们在特定物种中垂直遗传和固定；这一过程被称为内源性。慢病毒是包括艾滋病毒在内的一组哺乳动物逆转录病毒，已知可感染灵长类动物、反刍动物、马和猫。与许多其他逆转录病毒不同，这些病毒在生殖系渗透方面并没有明显成功。在这里，我们报告了在七种马达加斯加狐猴中发现内源性慢病毒插入的情况，这些狐猴来自两个不同的属-Cheirogaleus和Microcebus。结合分子时钟分析和同源插入的跨物种筛选，我们证明了这种内源性慢病毒在六个物种中的存在是大约420万年前发生的一次内源性事件的结果。此外，我们还证明了该慢病毒独立地渗透到了白纹伊蚊的种系中，并且这两种内源性事件几乎同时发生。使用多个前病毒拷贝，我们推导并表征了这种慢病毒的明显全长和完整的共识。这些结果提供了证据，证明慢病毒已经反复渗透到原猴物种的种系中，灵长类动物接触慢病毒的时间比根据流行的慢病毒序列所推断的要长得多。这项研究为重建祖先灵长类慢病毒的前所未有的机会奠定了基础，从而提高了我们对宿主与病毒相互作用的了解。逆转录病毒是一种RNA病毒，它被逆转录成DNA并插入宿主的基因组中。虽然这一过程最常发生在体细胞(例如艾滋病毒的免疫细胞)，但逆转录病毒偶尔也可以整合到宿主生殖细胞的基因组中。因此，这样的病毒插入可能会从父母垂直传播给后代，导致“内源性逆转录病毒”的形成。相当一部分哺乳动物基因组(在人类中约占8%)对应于内源性逆转录病毒在整个进化过程中整合的残留物，提供了过去病毒入侵的化石记录和关于现代逆转录病毒历史的重要线索。在这项研究中，我们证明了一种与HIV和其他慢病毒相关的内源性逆转录病毒在大约420万年前独立并几乎同时在马达加斯加狐猴的两个谱系中内源性。这是在灵长类动物中发现的第一种内源性慢病毒。基于从不同狐猴物种收集的序列，我们重建了这种祖先原猴慢病毒的表面完整和完整的序列，这将有助于功能分析，并促进我们对包括HIV在内的慢病毒的生物学和起源的理解。此外，我们的研究表明，慢病毒可能仍在狐猴中传播，对马达加斯加哺乳动物的系统筛查可以进一步加深我们对慢病毒过去和现在的多样性的了解。
Retroviruses normally infect the somatic cells of their host and are transmitted horizontally, i.e., in an exogenous way. Occasionally, however, some retroviruses can also infect and integrate into the genome of germ cells, which may allow for their vertical inheritance and fixation in a given species; a process known as endogenization. Lentiviruses, a group of mammalian retroviruses that includes HIV, are known to infect primates, ruminants, horses, and cats. Unlike many other retroviruses, these viruses have not been demonstrably successful at germline infiltration. Here, we report on the discovery of endogenous lentiviral insertions in seven species of Malagasy lemurs from two different genera—Cheirogaleus and Microcebus. Combining molecular clock analyses and cross-species screening of orthologous insertions, we show that the presence of this endogenous lentivirus in six species of Microcebus is the result of one endogenization event that occurred about 4.2 million years ago. In addition, we demonstrate that this lentivirus independently infiltrated the germline of Cheirogaleus and that the two endogenization events occurred quasi-simultaneously. Using multiple proviral copies, we derive and characterize an apparently full length and intact consensus for this lentivirus. These results provide evidence that lentiviruses have repeatedly infiltrated the germline of prosimian species and that primates have been exposed to lentiviruses for a much longer time than what can be inferred based on sequence comparison of circulating lentiviruses. The study sets the stage for an unprecedented opportunity to reconstruct an ancestral primate lentivirus and thereby advance our knowledge of host–virus interactions. Retroviruses are RNA viruses that are reverse transcribed into DNA and inserted into the host's genome. Though this process happens most frequently in somatic cells (e.g., immune cells for HIV), retroviruses can occasionally be integrated in the genome of the host's germ cells. Such viral insertions may thus be transmitted vertically from parent to offspring, leading to the formation of “endogenous retroviruses.” A substantial fraction of mammalian genomes (about 8% in humans) corresponds to remnants of endogenous retroviruses integrated throughout evolution, providing a fossil record of past viral invasions and important clues on the history of modern retroviruses. In this study, we demonstrate that an endogenous retrovirus related to HIV and other lentiviruses was endogenized independently and quasi-simultaneously in two lineages of Malagasy lemurs around 4.2 million years ago. These are the first endogenous lentiviruses discovered in primates. Based on sequences collected from different lemur species, we reconstructed an apparently intact and complete sequence for this ancestral prosimian lentivirus, which will allow functional analysis and advance our understanding of the biology and origin of lentiviruses, including HIV. Furthermore, our study indicates that lentiviruses may still be circulating in lemurs and that a systematic screening of Malagasy mammals could further our knowledge on the past and present diversity of lentiviruses.
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DOI：
10.1073/pnas.0307885100
发表时间：
2004-02-10
影响因子：
11.1
作者：
Hughes, JF;Coffin, JM
通讯作者：
Coffin, JM
影响因子：
4.1
作者：
Heckman, Kellie L.;Mariani, Carol L.;Yoder, Anne D.
通讯作者：
Yoder, Anne D.
DOI：
10.1073/pnas.0700471104
发表时间：
2007-04-10
影响因子：
11.1
作者：
Katzourakis, Aris;Tristem, Michael;Gifford, Robert J.
通讯作者：
Gifford, Robert J.
DOI：
10.1073/pnas.0806548105
发表时间：
2008-11-04
影响因子：
11.1
作者：
Pace, John K., II;Gilbert, Clement;Feschotte, Cedric
通讯作者：
Feschotte, Cedric
影响因子：
4
作者：
Gifford, Robert J.
通讯作者：
Gifford, Robert J.