GUANIDINE-SELECTED MUTANTS OF POLIOVIRUS - MAPPING OF POINT MUTATIONS TO POLYPEPTIDE 2C

GUANIDINE-SELECTED MUTANTS OF POLIOVIRUS - MAPPING OF POINT MUTATIONS TO POLYPEPTIDE 2C
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DOI:
10.1128/jvi.57.2.638-646.1986
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发表时间:
1986-02-01
影响因子:
5.4
通讯作者:
WIMMER, E
WIMMER, E
中科院分区:
医学2区
文献类型:
--
作者:
PINCUS, SE;DIAMOND, DC;WIMMER, E

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脊髓灰质炎病毒1型株间胍抗性和抗体抗性变体重组体的基因组RNA序列分析将能够在2.0 mM盐酸胍中生长的突变体的抗性定位于位于核苷酸4444 3“的区域。病毒基因组的这个区域指定非结构蛋白2C。确定了编码来自6个独立分离的耐2.0 mM胍突变体的2C的基因组RNA的序列。在所有情况下,所有6个分离株均在相同位置的2C中含有突变,导致两种类型的氨基酸变化。检查了依赖性突变体,发现每个突变体在2C内含有两个氨基酸变化。分离出对0.53 mM胍具有抗性的突变体,发现其缺乏在对2.0 mM胍具有抗性的变体中所见的突变。脊髓灰质炎病毒、口蹄疫病毒、鼻病毒2型和14型以及脑心肌炎病毒的2C蛋白的氨基酸序列的比较揭示了在总共115个残基的区域上的强同源性。在胍选择的突变体中观察到的所有突变都包含在该区域内。将在脊髓灰质炎病毒突变体中观察到的对2.0 mM胍具有抗性的突变的氨基酸区域与其他小核糖核酸病毒中的同源区域进行比较;发现在该位置存在的氨基酸与病毒对2.0 mM胍的敏感性之间存在强相关性。
Sequence analysis of the genomic RNA of interstrain guanidine-resistant and antibody-resistant variant recombinants of poliovirus type 1 mapped the resistance of mutants capable of growth in 2.0 mM guanidine hydrochloride to a region located 3'' of nucleotide 4444. This region of the viral genome specifies the nonstructural protein 2C. The sequence of genomic RNA encoding 2C from six independently isolated mutants resistant to 2.0 mM guanidine was determined. All six isolates contained a mutation in 2C at the same position in all cases, resulting in two types of amino acid changes. Dependent mutants were examined and found to contain two amino acid changes each within 2C. Mutants resistant to 0.53 mM guanidine were isolated and found to lack the mutations seen in variants resistant to 2.0 mM guanidine. A comparison of the amino acid sequences of the 2C proteins of poliovirus, foot-and-mouth disease virus, rhinovirus types 2 and 14, and encephalomyocarditis virus revealed a strong homology over regions totaling 115 residues. All of the mutations observed in guanidine-selected mutants were contained within this region. The amino acid region containing the mutations observed in poliovirus mutants resistant to 2.0 mM guanidine was compared with the homologous region in the other picornaviruses; a strong correlation was found between the amino acid present at this position and the sensitivity of the virus to 2.0 mM guanidine.