Department of Civil and Environmental Engineering, Graduate School of Engineering, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
J Virol. 2020 May 4;94(10). doi: 10.1128/JVI.02083-19.
RNA viruses form a dynamic distribution of mutant swarms (termed "quasispecies") due to the accumulation of mutations in the viral genome. The genetic diversity of a viral population is affected by several factors, including a bottleneck effect. Human-to-human transmission exemplifies a bottleneck effect, in that only part of a viral population can reach the next susceptible hosts. In the present study, two lineages of the rhesus rotavirus (RRV) strain of rotavirus A were serially passaged five times at a multiplicity of infection (MOI) of 0.1 or 0.001, and three phenotypes (infectious titer, cell binding ability, and specific growth rate) were used to evaluate the impact of a bottleneck effect on the RRV population. The specific growth rate values of lineages passaged under the stronger bottleneck (MOI of 0.001) were higher after five passages. The nucleotide diversity also increased, which indicated that the mutant swarms of the lineages under the stronger bottleneck effect were expanded through the serial passages. The random distribution of synonymous and nonsynonymous substitutions on rotavirus genome segments indicated that almost all mutations were selectively neutral. Simple simulations revealed that the presence of minor mutants could influence the specific growth rate of a population in a mutant frequency-dependent manner. These results indicate a stronger bottleneck effect can create more sequence spaces for minor sequences. In this study, we investigated a bottleneck effect on an RRV population that may drastically affect the viral population structure. RRV populations were serially passaged under two levels of a bottleneck effect, which exemplified human-to-human transmission. As a result, the genetic diversity and specific growth rate of RRV populations increased under the stronger bottleneck effect, which implied that a bottleneck created a new space in a population for minor mutants originally existing in a hidden layer, which includes minor mutations that cannot be distinguished from a sequencing error. The results of this study suggest that the genetic drift caused by a bottleneck in human-to-human transmission explains the random appearance of new genetic lineages causing viral outbreaks, which can be expected according to molecular epidemiology using next-generation sequencing in which the viral genetic diversity within a viral population is investigated.
RNA 病毒由于病毒基因组中突变的积累而形成突变体群体（称为“准种”）的动态分布。病毒种群的遗传多样性受多种因素影响，包括瓶颈效应。人与人之间的传播就是瓶颈效应的一个例子，因为只有部分病毒种群可以到达下一个易感宿主。在本研究中，我们对轮状病毒 A 的恒河猴轮状病毒（RRV）株的两个谱系进行了五次连续传代，感染复数（MOI）分别为 0.1 或 0.001，并用三种表型（感染滴度、细胞结合能力和特定生长率）来评估瓶颈效应对 RRV 种群的影响。在较强的瓶颈（MOI 为 0.001）下传代的谱系的特定生长率值在五次传代后更高。核苷酸多样性也增加了，这表明较强的瓶颈效应下的谱系突变体群体通过连续传代得到了扩展。轮状病毒基因组片段上同义和非同义替换的随机分布表明，几乎所有突变都是选择性中性的。简单的模拟表明，少数突变体的存在可以以突变频率依赖的方式影响群体的特定生长率。这些结果表明，较强的瓶颈效应可以为少数序列创造更多的序列空间。在本研究中，我们研究了 RRV 群体中的瓶颈效应，这可能会极大地影响病毒种群结构。RRV 群体在两种瓶颈效应水平下连续传代，这代表了人与人之间的传播。结果表明，较强的瓶颈效应下 RRV 群体的遗传多样性和特定生长率增加，这意味着瓶颈效应为原本存在于隐藏层中的少数突变体在群体中创造了一个新的空间，其中包括无法与测序错误区分开来的少数突变。本研究结果表明，人与人之间传播的瓶颈引起的遗传漂变解释了新遗传谱系随机出现导致病毒爆发的原因，这可以根据使用下一代测序进行的分子流行病学来预测，在该研究中，研究了病毒种群内的病毒遗传多样性。
