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首页> 外文期刊>Journal of Theoretical Biology >Evolutionary stable strategy: A test for theories of retroviral pathology which are based upon the concept of molecular mimicry [Review]
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Evolutionary stable strategy: A test for theories of retroviral pathology which are based upon the concept of molecular mimicry [Review]

机译：进化稳定策略：基于分子模拟概念的逆转录病毒病理学理论测试[综述]

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摘要

The genetic makeup of animal and plant populations is determined by established principles and concepts. Ecology and evolution provide a basic theoretical framework for understanding how genetic changes occur in populations. Whether these rules can be applied to host retroviral populations is unknown. Individuals infected with the human immunodeficiency virus (HIV) contain within their bodies a viral population. This population is known as a viral quasispecies. Located in the transmembrane protein of HIV-1 is the viral sequence Gly-Thr-Asp-Arg-Val. Previous immunological studies have shown that viral antibody is produced in response to this five-amino-acid sequence. Antibody to this viral sequence also crossreacts and binds to a related peptide sequence found on certain immune cells. This related sequence, Gly-Thr-Glu-Arg-Val, is found on immune cells bearing a structure known as the major histocompatibility complex (MHC). The viral transmembrane sequence, Gly-Thr-Asp-Arg-Val, can be substituted with alanine residues utilizing site-directed mutagenesis. This creates a viral clone devoid of the genetic similarity with the MHC. Chimpanzees progressing to AIDS contain both sequences of interest. Suppression of the chimpanzee quasispecies utilizing anti-retroviral drugs is proposed. This action serves to suppress the presence of the viruses containing the sequence Gly-Thr-Asp-Arg-Val. When viral load has been reduced significantly, a drug resistant, alanine altered clone is to be introduced in large numbers. The concept of evolutionary stable strategy predicts that a viable HIV clone with alanine residues can genetically dominate the viral population. Immune system recognition of the alanine sequence is likely to result in renewed antibody production. Antibodies to the alanine containing viral sequence should not recognize or bind to the MHC. Immunological parameters can then be measured to determine the physiological impact of eliminating a sequence responsible for molecular mimicry between virus and host. (C) 2000 Academic Press. [References: 110]
机译：动植物种群的遗传构成取决于既定的原则和概念。生态与进化为理解种群中遗传变化的发生提供了基本的理论框架。这些规则是否可以应用于宿主逆转录病毒种群尚不清楚。感染人类免疫缺陷病毒（HIV）的个体体内含有病毒种群。该种群被称为病毒准种。病毒序列Gly-Thr-Asp-Arg-Val位于HIV-1的跨膜蛋白中。先前的免疫学研究表明，对这种五氨基酸序列产生了病毒抗体。该病毒序列的抗体也与某些免疫细胞上发现的相关肽序列发生交叉反应并结合。在具有称为主要组织相容性复合体（MHC）的结构的免疫细胞上发现了这一相关序列Gly-Thr-Glu-Arg-Val。病毒跨膜序列Gly-Thr-Asp-Arg-Val可利用定点诱变替换为丙氨酸残基。这产生了与MHC缺乏遗传相似性的病毒克隆。进展为艾滋病的黑猩猩包含这两个感兴趣的序列。提出了利用抗逆转录病毒药物抑制黑猩猩准种的方法。该作用用于抑制含有序列Gly-Thr-Asp-Arg-Val的病毒的存在。当病毒载量显着降低时，将大量引入抗药性，丙氨酸改变的克隆。进化稳定策略的概念预测，带有丙氨酸残基的可行的HIV克隆可以在基因上主导病毒种群。丙氨酸序列的免疫系统识别可能会导致重新产生抗体。含有丙氨酸的病毒序列的抗体不应识别或结合MHC。然后可以测量免疫学参数，以确定消除造成病毒和宿主之间分子模拟的序列的生理影响。 （C）2000学术出版社。 [参考：110]

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