IDENTIFICATION OF A SINGLE AMINO-ACID RESIDUE IN THE CAPSID PROTEIN-VP1 OF COXSACKIEVIRUS-B4 THAT DETERMINES THE VIRULENT PHENOTYPE
IDENTIFICATION OF A SINGLE AMINO-ACID RESIDUE IN THE CAPSID PROTEIN-VP1 OF COXSACKIEVIRUS-B4 THAT DETERMINES THE VIRULENT PHENOTYPE
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DOI：
10.1128/jvi.67.8.4797-4803.1993
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发表时间：
1993-08-01
影响因子：
5.4
通讯作者：
RAMSINGH, A
中科院分区：
文献类型：
--
作者：
CAGGANA, M;CHAN, P;RAMSINGH, A
为了鉴定柯萨奇病毒 B4 毒力的分子决定因素，从强毒力病毒 CB4-V 和无毒力病毒 CB4-P 的 cDNA 克隆构建了一组重组嵌合病毒。最初的研究将毒力的主要决定因素映射到病毒基因组的 5' 端，其中包含 5' 非翻译区和 P1 区（A. Ramsingh、A. Hixson、B. Duceman 和 J. Slack, J. Virol. 64:3078-3081, 1990）。为了确定5'非翻译区是否导致毒力表型，在小鼠体内测试了在无毒背景下含有该毒力病毒区域的嵌合病毒（vCB403）。 vCB403构建体表现出与CB4-P相似的表型，表明5'非翻译区对毒力没有显着贡献。对 CB4-V 和 CB4-P 两者的 P1 区的序列数据的分析揭示了导致 VP1、VP2 和 VP4 中氨基酸取代的五种突变（A. Ramsingh、H. Araki、S. Bryant 和 A. Hixson，Virus Res. 23 :281-292, 1992)。对 VP1 和 VP2 中单个突变的分析表明，单个残基（VP1 的 Thr-129）决定了毒性表型。
To identify the molecular determinants of virulence for coxsackievirus B4, a panel of recombinant, chimeric viruses were constructed from cDNA clones of a virulent virus, CB4-V, and a nonvirulent virus, CB4-P. Initial studies mapped a major determinant of virulence to the 5' end of the viral genome, which contained the 5' untranslated and the Pl regions (A. Ramsingh, A. Hixson, B. Duceman, and J. Slack, J. Virol. 64:3078-3081, 1990). To determine whether the 5' untranslated region contributed to the virulent phenotype, a chimeric virus (vCB403) containing this region of the virulent virus on an avirulent background was tested in mice. The vCB403 construct displayed a phenotype similar to that of CB4-P, suggesting that the 5' untranslated region did not significantly contribute to virulence. Analysis of the sequence data of the Pl regions of both CB4-V and CB4-P revealed five mutations that resulted in amino acid substitutions in VP1, VP2, and VP4 (A. Ramsingh, H. Araki, S. Bryant, and A. Hixson, Virus Res. 23:281-292, 1992). Analysis of individual mutations in both VP1 and VP2 revealed that a single residue (Thr-129 of VP1) determined the virulent phenotype.