Sindbis virus pathogenesis: phenotypic reversion of an attenuated strain to virulence by second-site intragenic suppressor mutations.
Sindbis virus pathogenesis: phenotypic reversion of an attenuated strain to virulence by second-site intragenic suppressor mutations.
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辛德毕斯病毒发病机制：减毒株通过第二位点基因内抑制突变而表型回复毒力。
DOI：
10.1099/0022-1317-74-8-1691
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Johnston,RE
中科院分区：
文献类型：
--
作者：
Schoepp,RJ;Johnston,RE
辛德毕斯病毒E2糖蛋白E2c中和抗原位点特异性单克隆抗体（MAb）定义了影响新生小鼠毒力的致病结构域。E2c单克隆抗体逃逸突变体的序列分析表明，该结构域包括E2氨基酸62，96和159。发病机制域也受到E2位置114的变化的影响。E2残基Asn 62突变为Asp或Lys 159突变为Glu可抑制E2第114位Ser突变为Arg所导致的减毒表型。通过使用定点诱变来确定在E2位置62、114和159处带正电荷、带负电荷和不带电荷的氨基酸取代的特定组合的影响，研究了E2c发病结构域内表型抑制的可能机制。在E2氨基酸62或159处的第二位点抑制突变的表型毒力回复不依赖于与E2 114处的残基的离子相互作用。相反，抑制似乎是由特定残基介导的独立毒力效应的结果。
Monoclonal antibodies (MAbs) specific for the E2c neutralizing antigenic site on the Sindbis virus E2 glycoprotein define a pathogenesis domain that affects neonatal mouse virulence. Sequence analysis of E2c MAb escape mutants showed that the domain included E2 amino acids 62, 96 and 159. The pathogenesis domain is also influenced by changes at E2 position 114. Mutation of E2 residues Asn 62 to Asp or Lys 159 to Glu results in suppression of the attenuated phenotype conferred by a mutation from Ser to Arg at E2 position 114. Possible mechanisms of phenotypic suppression within the E2c pathogenesis domain were investigated by using site-directed mutagenesis to determine the effects of specific combinations of positively charged, negatively charged and uncharged amino acid substitutions at E2 positions 62, 114 and 159. Phenotypic reversion to virulence by second-site suppressor mutations at E2 amino acids 62 or 159 was not dependent on ionic interaction with the residue at E2 114. Rather, suppression appeared to be the result of independent virulence effects mediated by specific residues.