Insights into Theiler's virus neurovirulence based on a genomic comparison of the neurovirulent GDVII and less virulent BeAn strains.
Insights into Theiler's virus neurovirulence based on a genomic comparison of the neurovirulent GDVII and less virulent BeAn strains.
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基于神经毒力 GDVII 和毒力较低的 BeAn 毒株的基因组比较，深入了解泰勒病毒神经毒力。
DOI：
10.1016/0042-6822(88)90652-6
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发表时间：
1988
期刊：
影响因子：
3.7
通讯作者：
Lipton,HL
中科院分区：
文献类型：
--
作者：
Pevear,DC;Borkowski,J;Calenoff,M;Oh,CK;Ostrowski,B;Lipton,HL
泰勒氏小鼠脑脊髓炎病毒(TMEV)是一种自然存在的小鼠肠道病原体，主要根据其脑内接种后的神经毒力分为两个亚组：高毒力GDVII组和对毒力较低的毒株。为了开始阐明这两个TMEV亚组的神经毒力的分子基础，我们克隆并测定了高毒力GDVII病毒的全部8105个核苷酸的RNA基因组，并将其与毒力较低的Bean 8386病毒(D.C.Pevear，M.Calenoff，E.Rozhon和H.L.Lipton(1987)J.Viroll.61,1507-1516)进行了比较。这些病毒在核苷酸水平上有90.4%的同源性。核苷酸同源性最高的是RNAs的5‘和3’非编码区(分别为95.5%和99.2%)：这些区域被认为对控制病毒RNA合成、启动翻译、包膜和病毒粒子脱壳至关重要。菜豆病毒和GDVII病毒的2303个氨基酸在氨基酸水平上的同源性为95.7%(2303个残基中有99个不同)。其中39个氨基酸的差异发生在三个表面外壳蛋白中，VP1(20个差异)，VP2(10个差异)和VP3(9个差异)，而其余的变化分布在整个多蛋白中。尽管这些同一性水平太低，无法仅基于核苷酸序列分析来确定神经毒力图谱的位置，但拥有完整的序列将有助于构建用于此目的的重组Bean-GDVII病毒。
Theiler's murine encephalomyelitis viruses (TMEV) are naturally occurring enteric pathogens of mice which can be divided into two subgroups based primarily on their neurovirulence after intracerebral inoculation: the highly virulent GDVII group and the less virulent TO strains. To begin to elucidate the molecular basis of neurovirulence of the two TMEV subgroups, we have cloned and sequenced the entire 8105 nucleotide RNA genome of the highly virulent GDVII virus and compared it to the less virulent BeAn 8386 virus (D. C. Pevear, M. Calenoff, E. Rozhon, and H. L. Lipton (1987)J. Virol.61, 1507–1516). The viruses are 90.4% identical at the nucleotide level. The highest level of nucleotide identity is in the 5′ and 3′ noncoding regions of the RNAs (95.5 and 99.2%, respectively): regions believed to be important for control of viral RNA synthesis, initiation of translation, encapsidation, and virion uncoating. The 2303 amino acid polyproteins of BeAn and GDVII viruses are 95.7% identical at the amino acid level (99 of 2303 residues differed). Thirty-nine of these amino acid differences occur in the three surface coat proteins, VP1 (20 differences), VP2 (10 differences), and VP3 (9 differences), while the remainder of the changes are distributed throughout the polyprotein. Although these levels of identity are too low to determine where neurovirulence maps based solely on nucleotide sequence analysis, having the complete sequence will facilitate construction of recombinant BeAn-GDVII viruses to be used for this purpose.