COMPUTER-ASSISTED STUDY OF FUNCTIONS AND EVOLUTION OF LARGE DNA VIRUS GENOMES

大型 DNA 病毒基因组的功能和进化的计算机辅助研究

• 批准号: 3845124
• 负责人: E V KOONIN
• 金额: --
• 依托单位: NATIONAL LIBRARY OF MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3845124
• 关键词: DNA virus; Herpesviridae; Poxviridae; biochemical evolution; computer data analysis; gene deletion mutation; gene duplication; genome; helicase; microorganism growth; protein sequence; thymidylate kinase; transcription factor; virulence; virus genetics; virus protein

Computer-assisted comparisons of amino acid sequences of proteins of large DNA viruses with each other and with related cellular proteins were performed, with the emphasis on proteins that may specifically influence virus virulence. Vast collections of gene sequences of large DNA viruses are currently available, including one complete poxvirus genome and several herpesvirus genomes. The functions of a large fraction of proteins encoded by these viruses are not understood. Of particular interest are genes that are not essential for virus growth in tissue culture but influence virus virulence. A family of poxvirus proteins was described that contain two distinct domains similar to apparently unrelated cellular proteins. The N-terminal domain is related to similarly located domains of several transcription factors, and the C-terminal domain resembles a murine placental-specific protein MIPP. The latter domain consists of an array of four or five imperfect repeats. Our analysis revealed also truncated members of this protein family in poxviruses, suggesting a complex evolutionary pathway that might have involved duplications and deletions. Functions of several viral NTP-utilizing enzymes were predicted, including two poxvirus helicases and a putative NTPase that may be involved in virus maturation. A protein was identified in fowlpox virus that is related to mammalian cytidylate kinase and is proposed to possess the same enzymatic activity. A tentative phylogeny of viral and cellular thymidine and thymidylate kinases was generated and a hypothesis was developed that genes coding for enzymes of nucleotide metabolism could be acquired independently by different viruses via recombination with the respective cellular genes. A specific version of Zn finger motif was identified in a protein encoded by a gene of mousepox virus that has been sequenced in the Laboratory of Viral Diseases and has been shown to be essential for the virus to be virulent for its natural host. The comparative analysis of the Zn finger proteins of the respective family is in progress.

蛋白质氨基酸序列的计算机辅助比较 大的DNA病毒之间以及与相关的细胞蛋白质之间的相互作用， 进行，重点是蛋白质，可能具体影响 病毒毒力 大型DNA病毒基因序列的大量集合 包括一个完整的痘病毒基因组， 几种疱疹病毒基因组。 一大部分的功能 由这些病毒编码的蛋白质尚不清楚。 特别 感兴趣是对组织中病毒生长不是必需的基因 培养，但影响病毒毒力。 痘病毒蛋白质的一个家族， 描述包含两个不同的域， 不相关的细胞蛋白质。 N端结构域与 几种转录因子的相似定位结构域， C-末端结构域类似于鼠胎盘特异性蛋白MIPP。 后一个结构域由四个或五个不完全重复序列组成。 我们的分析还揭示了在大肠杆菌中该蛋白家族的截短成员。 痘病毒，这表明一个复杂的进化途径， 涉及重复和删除。 几种病毒的功能 预测了利用NTP的酶，包括两个痘病毒解旋酶 和一个可能参与病毒成熟的推定NTR。 一 在鸡痘病毒中鉴定出一种与哺乳动物相关的蛋白 胞苷酸激酶，并被认为具有相同的酶活性。 病毒和细胞胸苷和胸苷酸的初步研究 产生了激酶，并提出了一个假设，即编码 对于核苷酸代谢酶可以独立获得， 不同的病毒通过与各自的细胞基因重组。 在一个编码的蛋白质中发现了一个特定形式的锌指基序， 由鼠痘病毒的一个基因组成， 病毒性疾病，并已被证明是必不可少的病毒， 对它的自然宿主是致命的 锌指的比较分析 各家族的蛋白质正在进行中。