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树鼩腺病毒基因组的分子解剖学;病毒基因的进化与病毒系统发育

Molecular anatomy of Tupaia (tree shrew) adenovirus genome; evolution of viral genes and viral phylogeny.

作者信息

Bahr Udo, Schöndorf Eva, Handermann Michaela, Darai Gholamreza

机构信息

Hygiene-Institute, Department of Virology, University of Heidelberg, Im Neuenheimer Feld 324, D-69120 Heidelberg, Federal Republic of Germany.

出版信息

Virus Genes. 2003 Aug;27(1):29-48. doi: 10.1023/a:1025120418159.

DOI:10.1023/a:1025120418159
PMID:12913356
Abstract

Adenoviruses are globally spread and infect species in all five taxons of vertebrates. Outstanding attention is focused on adenoviruses because of their transformation potential, their possible usability as vectors in gene therapy and their applicability in studies dealing with, e.g. cell cycle control, DNA replication, transcription, splicing, virus-host interactions, apoptosis, and viral evolution. The accumulation of genetic data provides the basis for the increase of our knowledge about adenoviruses. The Tupaia adenovirus (TAV) infects members of the genus Tupaiidae that are frequently used as laboratory animals in behavior research dealing with questions about biological and molecular processes of stress in mammals, in neurobiological and physiological studies, and as model organisms for human hepatitis B and C virus infections. In the present study the TAV genome underwent an extensive analysis including determination of codon usage, CG depletion, gene content, gene arrangement, potential splice sites, and phylogeny. The TAV genome has a length of 33,501 bp with a G+C content of 49.96%. The genome termini show a strong CG depletion that could be due to methylation of these genome regions during the viral replication cycle. The analysis of the coding capacity of the complete TAV genome resulted in the identification of 109 open reading frames (ORFs), of which 38 were predicted to be real viral genes. TAV was classified within the genus Mastadenovirus characterized by typical gene content, arrangement, and homology values of 29 conserved ORFs. Phylogenetic trees show that TAV is part of a separate evolutionary lineage and no mastadenovirus species can be considered as the most related. In contrast to other mastadenoviruses a direct ancestor of TAV captured a DUT gene from its mammalian host, presumably controlling local dUTP levels during replication and enhance viral replication in non-dividing host tissues. Furthermore, TAV possesses a second DNA-binding protein gene, that is likely to play a role in the determination of the host range. In view of these data it is conceivable that TAV underwent evolutionary adaptations to its biological environment resulting in the formation of special genomic components that provided TAV with the ability to expand its host range during viral evolution.

摘要

腺病毒在全球广泛传播,可感染脊椎动物所有五个分类单元中的物种。由于其转化潜力、在基因治疗中作为载体的可能用途以及在例如细胞周期控制、DNA复制、转录、剪接、病毒-宿主相互作用、细胞凋亡和病毒进化等研究中的适用性,腺病毒受到了特别关注。遗传数据的积累为我们增加对腺病毒的了解提供了基础。树鼩腺病毒(TAV)感染树鼩科成员,树鼩科动物在涉及哺乳动物应激的生物学和分子过程问题的行为研究、神经生物学和生理学研究中经常被用作实验动物,并且作为人类乙型和丙型肝炎病毒感染的模式生物。在本研究中,对TAV基因组进行了广泛分析,包括密码子使用情况、CG缺失、基因含量、基因排列、潜在剪接位点和系统发育的测定。TAV基因组长度为33,501 bp,G+C含量为49.96%。基因组末端显示出强烈的CG缺失,这可能是由于这些基因组区域在病毒复制周期中发生了甲基化。对完整TAV基因组编码能力的分析导致鉴定出109个开放阅读框(ORF),其中38个被预测为真正的病毒基因。TAV被归类于哺乳动物腺病毒属,其特征在于典型的基因含量、排列以及29个保守ORF的同源性值。系统发育树表明,TAV是一个独立进化谱系的一部分,没有任何哺乳动物腺病毒物种可被视为与其关系最密切的物种。与其他哺乳动物腺病毒不同,TAV的一个直接祖先从其哺乳动物宿主捕获了一个DUT基因,推测该基因在复制过程中控制局部dUTP水平,并增强在非分裂宿主组织中的病毒复制。此外,TAV拥有第二个DNA结合蛋白基因,该基因可能在宿主范围的确定中发挥作用。鉴于这些数据,可以想象TAV对其生物环境进行了进化适应,导致形成了特殊的基因组成分,使TAV在病毒进化过程中具有扩大其宿主范围的能力。

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