Yoshihara Keisuke, Le Minh Nhat, Nagasawa Koo, Tsukagoshi Hiroyuki, Nguyen Hien Anh, Toizumi Michiko, Moriuchi Hiroyuki, Hashizume Masahiro, Ariyoshi Koya, Dang Duc Anh, Kimura Hirokazu, Yoshida Lay-Myint
Department of Paediatric Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan; Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan.
Department of Paediatric Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan; National Institute of Hygiene and Epidemiology, Hanoi, Vietnam.
Infect Genet Evol. 2016 Nov;45:437-446. doi: 10.1016/j.meegid.2016.10.010. Epub 2016 Oct 14.
We performed molecular evolutionary analyses of the G gene C-terminal 3rd hypervariable region of RSV-A genotypes NA1 and ON1 strains from the paediatric acute respiratory infection patients in central Vietnam during the 2010-2012 study period. Time-scaled phylogenetic analyses were performed using Bayesian Markov Chain Monte Carlo (MCMC) method, and pairwise distances (p-distances) were calculated. Bayesian Skyline Plot (BSP) was constructed to analyze the time-trend relative genetic diversity of central Vietnam RSV-A strains. We also estimated the N-glycosylation sites within G gene hypervariable region. Amino acid substitutions under positive and negative selection pressure were examined using Conservative Single Likelihood Ancestor Counting (SLAC), Fixed Effects Likelihood (FEL), Internal Fixed Effects Likelihood (IFEL) and Mixed Effects Model for Episodic Diversifying Selection (MEME) models. The majority of central Vietnam ON1 strains detected in 2012 were classified into lineage 1 with few positively selected substitutions. As for the Vietnamese NA1 strains, four lineages were circulating during the study period with a few positive selection sites. Shifting patterns of the predominantly circulating NA1 lineage were observed in each year during the investigation period. Median p-distance of central Vietnam NA1 strains was wider (p-distance=0.028) than that of ON1 (p-distance=0.012). The molecular evolutionary rate of central Vietnam ON1 strains was estimated to be 2.55×10 (substitutions/site/year) and was faster than NA1 (7.12×10 (substitutions/site/year)). Interestingly, the evolutionary rates of both genotypes ON1 and NA1 strains from central Vietnam were faster than the global strains respectively. Furthermore, the shifts of N-glycosylation pattern within the G gene 3rd hypervariable region of Vietnamese NA1 strains were observed in each year. BSP analysis indicated the rapid growth of RSV-A effective population size in early 2012. These results suggested that the molecular evolution of RSV-A G gene detected in central Vietnam was fast with unique evolutionary dynamics.
在2010 - 2012年研究期间，我们对越南中部儿科急性呼吸道感染患者的呼吸道合胞病毒A组（RSV-A）基因型NA1和ON1毒株的G基因C端第3高变区进行了分子进化分析。使用贝叶斯马尔可夫链蒙特卡罗（MCMC）方法进行了时间尺度系统发育分析，并计算了成对距离（p距离）。构建了贝叶斯天际线图（BSP）以分析越南中部RSV-A毒株的时间趋势相对遗传多样性。我们还估计了G基因高变区内的N-糖基化位点。使用保守单似然祖先计数（SLAC）、固定效应似然（FEL）、内部固定效应似然（IFEL）和 episodic多样化选择混合效应模型（MEME）模型检查了正选择和负选择压力下的氨基酸替换。2012年检测到的越南中部大多数ON1毒株被归类为谱系1，仅有少数正选择替换。至于越南NA1毒株，在研究期间有四个谱系在传播，有一些正选择位点。在调查期间的每年都观察到主要传播的NA1谱系的变化模式。越南中部NA1毒株的中位p距离（p距离 = 0.028）比ON毒株的（p距离 = 0.012）更宽。越南中部ON1毒株的分子进化速率估计为2.55×10（替换/位点/年），比NA1毒株（7.12×10（替换/位点/年））更快。有趣的是，越南中部的ON1和NA1基因型毒株的进化速率分别比全球毒株更快。此外，每年都观察到越南NA1毒株G基因第3高变区内N-糖基化模式的变化。BSP分析表明2012年初RSV-A有效种群大小迅速增长。这些结果表明，在越南中部检测到的RSV-A G基因的分子进化很快，具有独特的进化动态。
