From Resistance to Stimulation: the Evolution of a Virus in the Presence of a Dominant Lethal Inhibitory Scaffolding Protein
From Resistance to Stimulation: the Evolution of a Virus in the Presence of a Dominant Lethal Inhibitory Scaffolding Protein
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从抵抗到刺激：在显性致死抑制支架蛋白存在下病毒的进化
DOI：
10.1128/jvi.00261-11
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发表时间：
2011
影响因子：
5.4
通讯作者：
B. Fane
中科院分区：
文献类型：
--
作者：
James E. Cherwa;B. Fane
通过获得对抑制剂的抗性，病毒可以变得依赖于该抑制剂以获得最佳适应度。然而，抑制剂很少，如果有的话，刺激抗性菌株的适应度值等于或超过未受抑制的野生型水平。这将需要一种自适应机制，将抑制剂转化为有益的复制因子。使用质粒编码的抑制外部支架蛋白阻断φX174组装，我们先前证明了这种机制是可能的。抗性菌株，被称为进化菌株，包含四种有助于抗性表型的突变。三个突变导致外壳蛋白的替换，而第四个突变改变了病毒编码的外部支架蛋白。为了确定抑制蛋白的刺激是否与抗性共同进化，还是在抗性牢固建立后获得，我们分离并鉴定了暂时先于先前表征的突变株的菌株，称为中间菌株。分析结果表明，病毒编码的外部支架蛋白突变是刺激菌株适合度的主要原因。当这种突变被置于野生型背景中时，它不会产生抗性。该突变也与质粒编码的显性致死突变呈顺式排列。在这种结构中，无论感染病毒的基因型（野生型、进化型或中间型）如何，刺激突变都没有表现出活性。因此，随着外壳蛋白突变，刺激需要两个外部支架蛋白基因：一次抑制基因和进化过程中获得的突变基因。
ABSTRACT By acquiring resistance to an inhibitor, viruses can become dependent on that inhibitor for optimal fitness. However, inhibitors rarely, if ever, stimulate resistant strain fitness to values that equal or exceed the uninhibited wild-type level. This would require an adaptive mechanism that converts the inhibitor into a beneficial replication factor. Using a plasmid-encoded inhibitory external scaffolding protein that blocks φX174 assembly, we previously demonstrated that such mechanisms are possible. The resistant strain, referred to as the evolved strain, contains four mutations contributing to the resistance phenotype. Three mutations confer substitutions in the coat protein, whereas the fourth mutation alters the virus-encoded external scaffolding protein. To determine whether stimulation by the inhibitory protein coevolved with resistance or whether it was acquired after resistance was firmly established, the strain temporally preceding the previously characterized mutant, referred to as the intermediary strain, was isolated and characterized. The results of the analysis indicated that the mutation in the virus-encoded external scaffolding protein was primarily responsible for stimulating strain fitness. When the mutation was placed in a wild-type background, it did not confer resistance. The mutation was also placed in cis with the plasmid-encoded dominant lethal mutation. In this configuration, the stimulating mutation exhibited no activity, regardless of the genotype (wild type, evolved, or intermediary) of the infecting virus. Thus, along with the coat protein mutations, stimulation required two external scaffolding protein genes: the once inhibitory gene and the mutant gene acquired during evolution.
耐药单纯疱疹病毒 1 突变体的体内适应性和毒力。
DOI：
10.1099/vir.0.82787-0
发表时间：
2007
期刊：
The Journal of general virology
影响因子：
--
作者：
Pesola,JeanM;Coen,DonaldM
通讯作者：
Coen,DonaldM