Discovery and Characterization of Mammalian Endogenous Parvoviruses
Discovery and Characterization of Mammalian Endogenous Parvoviruses
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DOI：
10.1128/jvi.01732-10
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发表时间：
2010-12-01
影响因子：
5.4
通讯作者：
Lipkin, W. Ian
中科院分区：
文献类型：
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作者：
Kapoor, Amit;Simmonds, Peter;Lipkin, W. Ian
核苷酸序列的公共数据库包含来自哺乳动物基因组的呈指数增长的序列数据量。通过大规模生物信息学筛选与外源性哺乳动物病毒同源的序列，我们在几种哺乳动物（包括大鼠、沙袋鼠、负鼠、豚鼠、刺猬、非洲象和欧洲兔）的基因组中发现了与细小病毒属和依赖病毒属中的人和动物细小病毒（PV）相关的几个序列。然而，这些内源性细小病毒（EnPV）序列的系统发育分析表明，外源性哺乳动物PV的特点，迄今为止，大量的遗传差异。从大鼠（褐家鼠）基因组DNA中扩增了一种新型EnPV的整个非结构基因和衣壳基因序列，并进行了遗传学特征分析。大鼠EnPV序列与细小病毒属成员的关系最密切，与犬细小病毒的非结构蛋白和衣壳蛋白的氨基酸同源性分别为>70%和65%。通过PCR克隆和病毒和染色体连接处的序列分析证实EnPV整合到大鼠的5号染色体中。使用反向PCR，我们确定，大鼠基因组包含一个单一的副本，大鼠EnPV。考虑到哺乳动物的遗传学，我们估计EnPV整合到大鼠基因组不到30万年前。使用所有已知的代表性外源细小病毒（ExPV）和EnPV序列进行的比较系统发育分析显示EnPV的两个主要遗传组，一个遗传上与细小病毒属更相似，另一个遗传上与依赖病毒属更相似。只有在更广泛的动物纲、目和种的完整基因组序列可用时，才能认识到在哺乳动物和其他脊椎动物进化过程中经历内源化的细小病毒的遗传多样性的全部程度。
Public databases of nucleotide sequences contain exponentially increasing amounts of sequence data from mammalian genomes. Through the use of large-scale bioinformatic screening for sequences homologous to exogenous mammalian viruses, we found several sequences related to human and animal parvoviruses (PVs) in the Parvovirus and Dependovirus genera within genomes of several mammals, including rats, wallabies, opossums, guinea pigs, hedgehogs, African elephants, and European rabbits. However, phylogenetic analysis of these endogenous parvovirus (EnPV) sequences demonstrated substantial genetic divergence from exogenous mammalian PVs characterized to date. Entire nonstructural and capsid gene sequences of a novel EnPV were amplified and genetically characterized from rat (Rattus norvegicus) genomic DNA. Rat EnPV sequences were most closely related to members of the genus Parvovirus, with >70% and 65% amino acid identities to nonstructural and capsid proteins of canine parvovirus, respectively. Integration of EnPV into chromosome 5 of rats was confirmed by PCR cloning and sequence analysis of the viral and chromosomal junctions. Using inverse PCR, we determined that the rat genome contains a single copy of rat EnPV. Considering mammalian phylogeny, we estimate that EnPV integrated into the rat genome less than 30 million years ago. Comparative phylogenetic analysis done using all known representative exogenous parvovirus (ExPV) and EnPV sequences showed two major genetic groups of EnPVs, one genetically more similar to genus Parvovirus and the other genetically more similar to the genus Dependovirus. The full extent of the genetic diversity of parvoviruses that have undergone endogenization during evolution of mammals and other vertebrates will be recognized only once complete genomic sequences from a wider range of classes, orders, and species of animals become available.