Evolution of circulating wild poliovirus and of vaccine-derived poliovirus in an immunodeficient patient: a unifying model
Evolution of circulating wild poliovirus and of vaccine-derived poliovirus in an immunodeficient patient: a unifying model
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DOI：
10.1128/jvi.74.16.7381-7390.2000
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发表时间：
2000-08-01
影响因子：
5.4
通讯作者：
Agol, VI
中科院分区：
文献类型：
--
作者：
Gavrilin, GV;Cherkasova, EA;Agol, VI
我们确定了VP1和2AB基因的核苷酸序列和部分的2C和3D基因的两个不断发展的脊髓灰质炎病毒谱系：T地理型和Sabin疫苗衍生的分离株从免疫缺陷患者的野生病毒的循环。发现病毒RNA的不同区域不同步进化，并且疫苗衍生群体中2AB区域的进化速率在其整个历史中并不恒定。同义替换的发生并不完全随机，这表明需要保护某些稀有密码子（可能是为了控制翻译延伸），以及病毒RNA结构中存在未识别的限制。然而，对两个谱系进化的主要贡献来自同义替换的线性积累。因此，与目前的病毒进化理论相一致，我们认为，这两个谱系中的大多数突变是固定的，因为从异质群体中连续采样的随机部分主要含有中性和可能的不利突变。作为这种进化模式的结果，病毒适应性可以保持在或多或少的恒定水平，或者可以降低，除非随机产生更适合的变体。所提出的脊髓灰质炎病毒自然进化的统一模型对脊髓灰质炎的流行病学具有重要意义。
We determined nucleotide sequences of the VP1 and 2AB genes and portions of the 2C and 3D genes of two evolving poliovirus lineages: circulating wild viruses of T geotype and Sabin vaccine-derived isolates from an immunodeficient patient. Different regions of the viral RNA were found to evolve nonsynchronously, and the rate of evolution of the 2AB region in the vaccine-derived population was not constant throughout its history. Synonymous replacements occurred not completely randomly, suggesting the need for conservation of certain rare codons (possibly to control translation elongation) and the existence of unidentified constraints in the viral RNA structure. Nevertheless the major contribution to the evolution of the two lineages came from linear accumulation of synonymous substitutions. Therefore, in agreement with current theories of viral evolution, we suggest that the majority of the mutations in both lineages were fixed as a result of successive sampling, from the heterogeneous populations, of random portions containing predominantly neutral and possibly adverse mutations. As a result of such a mode of evolution, the virus fitness may be maintained at a more or less constant level or may decrease unless more-fit variants are stochastically generated. The proposed unifying model of natural poliovirus evolution has important implications for the epidemiology of poliomyelitis.