甲型H1N1流行性感冒病毒血凝素蛋白基因进化研究

推算全球各地近年来分离的甲型H1N1流行性感冒(简称流感)病毒株血凝素(HA)蛋白片段的进化速率和进化分歧时间,从而初步探索流感病毒的起源和传播关系.方法搜集GenBank数据库中2008年以来登录的全球流感病毒H1序列共344条(人源性248条,猪源性84条,禽源性11条,其他1条)及本课题组分离的7条人源性H1序列,按照"分子钟"进化理论和基于markov chain monte carlo(MCMC)算法的Bayesian推断方法估算进化速率和进化分歧时间,并利用后验概率方法构建系统进化树.结果 系统进化树显示,美国人源性、猪源性与禽源性H1序列与部分亚洲猪源性H1序列构成一个主要分支(美国分支);全球其他地区的人源性H1序列构成另一个主要分支(欧亚人分支);而部分中国猪源性、禽源性H1序列与意大利分离的禽源性序列也构成一个分支(欧亚动物分支).全球H1N1和H1N2流感病毒株H1序列930 bp核苷酸序列的年平均进化速率约为2.57×10-3/位点(95%最高后验概率区间:1.96×10-33.03×10-3/位点).其中,欧洲人源性H1序列和中国大陆猪H1序列的起源时间最早,年进化速率分别为6.46×10-3/位点、0.97×10-3/位点;而美国的人源性与猪源性H1序列的起源时间相近,年进化速率则分别为5.86×10-3/位点、5.02×10-3/位点.结论 本次甲型H1N1流感暴发是北美地区H1N1病毒株长期人畜共患性积累的基因变异所致.中国大陆地区并非本次流感疫情病毒株的发源地,尚无证据能够表明北美暴发株属于一个全新的流感病毒变种.     

甲型H1N1流行性感冒病毒血凝素蛋白基因进化研究

Objective To determine the evolutionary rate and divergence time of influenza A virus HA gene isolated recently worldwide pandemic and explore the origin and its transmission. Methods A total of 344 HI sequences available in the GenBank (including 248 isolated from human, 84 from swine, 11 from avian, and 1 from ferret) and 7 isolated in Shanghai were collected. The nucleotide substitution rate and time to most recent common ancestor (tMRCA) was calculated using molecular clock theory and Bayesian Skyline Plot (BSP) based on Markov chain Monte Carlo. Then genetic phylogeny was constructed referring to posterior distribution. Results It was found that H1 sequences in the US from human, swine and avian were clustered significantly with swine H1 ones from Asia phylogenetieally (Cluster US). The second cluster (Cluster Eurasian Human) nearly consisted of human H1 sequences isolated in other regions. The third cluster (Cluster Eurasian Animal) consisted of swine and avian H1 sequences from China and Italy respectively. As for all the H1 sequences, the evolutionary rate was of 2.57×10-3substitutions/site per year averagely (95% Highest Posterior Density: 1.96×10-3-3.03×10-3/site per year). The estimated dates for tMRCA of human H1 in Europe and swine H1 in the mainland of China were the earliest, with the corresponding rates of 6.46×10-3/site per year and 0.97×10-3/site per year respectively. The tMRCAs of human and swine H1 sequences from the US were similar, with the rates of 5.86×10-3/site per year and 5.02×10-3/site per year. Conclusion The present flu outbreak was possibly induced by long-term circulation of influenza A virus (H1 N1) in human population and swine herds in America. There was no evidence proving that influenza virus in China involved in the present outbreak.     

甲型H1N1流行性感冒病毒血凝素蛋白基因进化研究

Objective To determine the evolutionary rate and divergence time of influenza A virus HA gene isolated recently worldwide pandemic and explore the origin and its transmission. Methods A total of 344 HI sequences available in the GenBank (including 248 isolated from human, 84 from swine, 11 from avian, and 1 from ferret) and 7 isolated in Shanghai were collected. The nucleotide substitution rate and time to most recent common ancestor (tMRCA) was calculated using molecular clock theory and Bayesian Skyline Plot (BSP) based on Markov chain Monte Carlo. Then genetic phylogeny was constructed referring to posterior distribution. Results It was found that H1 sequences in the US from human, swine and avian were clustered significantly with swine H1 ones from Asia phylogenetieally (Cluster US). The second cluster (Cluster Eurasian Human) nearly consisted of human H1 sequences isolated in other regions. The third cluster (Cluster Eurasian Animal) consisted of swine and avian H1 sequences from China and Italy respectively. As for all the H1 sequences, the evolutionary rate was of 2.57×10-3substitutions/site per year averagely (95% Highest Posterior Density: 1.96×10-3-3.03×10-3/site per year). The estimated dates for tMRCA of human H1 in Europe and swine H1 in the mainland of China were the earliest, with the corresponding rates of 6.46×10-3/site per year and 0.97×10-3/site per year respectively. The tMRCAs of human and swine H1 sequences from the US were similar, with the rates of 5.86×10-3/site per year and 5.02×10-3/site per year. Conclusion The present flu outbreak was possibly induced by long-term circulation of influenza A virus (H1 N1) in human population and swine herds in America. There was no evidence proving that influenza virus in China involved in the present outbreak.     

甲型H1N1流行性感冒病毒血凝素蛋白基因进化研究

Objective To determine the evolutionary rate and divergence time of influenza A virus HA gene isolated recently worldwide pandemic and explore the origin and its transmission. Methods A total of 344 HI sequences available in the GenBank (including 248 isolated from human, 84 from swine, 11 from avian, and 1 from ferret) and 7 isolated in Shanghai were collected. The nucleotide substitution rate and time to most recent common ancestor (tMRCA) was calculated using molecular clock theory and Bayesian Skyline Plot (BSP) based on Markov chain Monte Carlo. Then genetic phylogeny was constructed referring to posterior distribution. Results It was found that H1 sequences in the US from human, swine and avian were clustered significantly with swine H1 ones from Asia phylogenetieally (Cluster US). The second cluster (Cluster Eurasian Human) nearly consisted of human H1 sequences isolated in other regions. The third cluster (Cluster Eurasian Animal) consisted of swine and avian H1 sequences from China and Italy respectively. As for all the H1 sequences, the evolutionary rate was of 2.57×10-3substitutions/site per year averagely (95% Highest Posterior Density: 1.96×10-3-3.03×10-3/site per year). The estimated dates for tMRCA of human H1 in Europe and swine H1 in the mainland of China were the earliest, with the corresponding rates of 6.46×10-3/site per year and 0.97×10-3/site per year respectively. The tMRCAs of human and swine H1 sequences from the US were similar, with the rates of 5.86×10-3/site per year and 5.02×10-3/site per year. Conclusion The present flu outbreak was possibly induced by long-term circulation of influenza A virus (H1 N1) in human population and swine herds in America. There was no evidence proving that influenza virus in China involved in the present outbreak.     

甲型H1N1流行性感冒病毒血凝素蛋白基因进化研究

Objective To determine the evolutionary rate and divergence time of influenza A virus HA gene isolated recently worldwide pandemic and explore the origin and its transmission. Methods A total of 344 HI sequences available in the GenBank (including 248 isolated from human, 84 from swine, 11 from avian, and 1 from ferret) and 7 isolated in Shanghai were collected. The nucleotide substitution rate and time to most recent common ancestor (tMRCA) was calculated using molecular clock theory and Bayesian Skyline Plot (BSP) based on Markov chain Monte Carlo. Then genetic phylogeny was constructed referring to posterior distribution. Results It was found that H1 sequences in the US from human, swine and avian were clustered significantly with swine H1 ones from Asia phylogenetieally (Cluster US). The second cluster (Cluster Eurasian Human) nearly consisted of human H1 sequences isolated in other regions. The third cluster (Cluster Eurasian Animal) consisted of swine and avian H1 sequences from China and Italy respectively. As for all the H1 sequences, the evolutionary rate was of 2.57×10-3substitutions/site per year averagely (95% Highest Posterior Density: 1.96×10-3-3.03×10-3/site per year). The estimated dates for tMRCA of human H1 in Europe and swine H1 in the mainland of China were the earliest, with the corresponding rates of 6.46×10-3/site per year and 0.97×10-3/site per year respectively. The tMRCAs of human and swine H1 sequences from the US were similar, with the rates of 5.86×10-3/site per year and 5.02×10-3/site per year. Conclusion The present flu outbreak was possibly induced by long-term circulation of influenza A virus (H1 N1) in human population and swine herds in America. There was no evidence proving that influenza virus in China involved in the present outbreak.     

甲型H1N1流行性感冒病毒血凝素蛋白基因进化研究

Objective To determine the evolutionary rate and divergence time of influenza A virus HA gene isolated recently worldwide pandemic and explore the origin and its transmission. Methods A total of 344 HI sequences available in the GenBank (including 248 isolated from human, 84 from swine, 11 from avian, and 1 from ferret) and 7 isolated in Shanghai were collected. The nucleotide substitution rate and time to most recent common ancestor (tMRCA) was calculated using molecular clock theory and Bayesian Skyline Plot (BSP) based on Markov chain Monte Carlo. Then genetic phylogeny was constructed referring to posterior distribution. Results It was found that H1 sequences in the US from human, swine and avian were clustered significantly with swine H1 ones from Asia phylogenetieally (Cluster US). The second cluster (Cluster Eurasian Human) nearly consisted of human H1 sequences isolated in other regions. The third cluster (Cluster Eurasian Animal) consisted of swine and avian H1 sequences from China and Italy respectively. As for all the H1 sequences, the evolutionary rate was of 2.57×10-3substitutions/site per year averagely (95% Highest Posterior Density: 1.96×10-3-3.03×10-3/site per year). The estimated dates for tMRCA of human H1 in Europe and swine H1 in the mainland of China were the earliest, with the corresponding rates of 6.46×10-3/site per year and 0.97×10-3/site per year respectively. The tMRCAs of human and swine H1 sequences from the US were similar, with the rates of 5.86×10-3/site per year and 5.02×10-3/site per year. Conclusion The present flu outbreak was possibly induced by long-term circulation of influenza A virus (H1 N1) in human population and swine herds in America. There was no evidence proving that influenza virus in China involved in the present outbreak.     

甲型H1N1流行性感冒病毒血凝素蛋白基因进化研究

Objective To determine the evolutionary rate and divergence time of influenza A virus HA gene isolated recently worldwide pandemic and explore the origin and its transmission. Methods A total of 344 HI sequences available in the GenBank (including 248 isolated from human, 84 from swine, 11 from avian, and 1 from ferret) and 7 isolated in Shanghai were collected. The nucleotide substitution rate and time to most recent common ancestor (tMRCA) was calculated using molecular clock theory and Bayesian Skyline Plot (BSP) based on Markov chain Monte Carlo. Then genetic phylogeny was constructed referring to posterior distribution. Results It was found that H1 sequences in the US from human, swine and avian were clustered significantly with swine H1 ones from Asia phylogenetieally (Cluster US). The second cluster (Cluster Eurasian Human) nearly consisted of human H1 sequences isolated in other regions. The third cluster (Cluster Eurasian Animal) consisted of swine and avian H1 sequences from China and Italy respectively. As for all the H1 sequences, the evolutionary rate was of 2.57×10-3substitutions/site per year averagely (95% Highest Posterior Density: 1.96×10-3-3.03×10-3/site per year). The estimated dates for tMRCA of human H1 in Europe and swine H1 in the mainland of China were the earliest, with the corresponding rates of 6.46×10-3/site per year and 0.97×10-3/site per year respectively. The tMRCAs of human and swine H1 sequences from the US were similar, with the rates of 5.86×10-3/site per year and 5.02×10-3/site per year. Conclusion The present flu outbreak was possibly induced by long-term circulation of influenza A virus (H1 N1) in human population and swine herds in America. There was no evidence proving that influenza virus in China involved in the present outbreak.     

甲型H1N1流行性感冒病毒血凝素蛋白基因进化研究

Objective To determine the evolutionary rate and divergence time of influenza A virus HA gene isolated recently worldwide pandemic and explore the origin and its transmission. Methods A total of 344 HI sequences available in the GenBank (including 248 isolated from human, 84 from swine, 11 from avian, and 1 from ferret) and 7 isolated in Shanghai were collected. The nucleotide substitution rate and time to most recent common ancestor (tMRCA) was calculated using molecular clock theory and Bayesian Skyline Plot (BSP) based on Markov chain Monte Carlo. Then genetic phylogeny was constructed referring to posterior distribution. Results It was found that H1 sequences in the US from human, swine and avian were clustered significantly with swine H1 ones from Asia phylogenetieally (Cluster US). The second cluster (Cluster Eurasian Human) nearly consisted of human H1 sequences isolated in other regions. The third cluster (Cluster Eurasian Animal) consisted of swine and avian H1 sequences from China and Italy respectively. As for all the H1 sequences, the evolutionary rate was of 2.57×10-3substitutions/site per year averagely (95% Highest Posterior Density: 1.96×10-3-3.03×10-3/site per year). The estimated dates for tMRCA of human H1 in Europe and swine H1 in the mainland of China were the earliest, with the corresponding rates of 6.46×10-3/site per year and 0.97×10-3/site per year respectively. The tMRCAs of human and swine H1 sequences from the US were similar, with the rates of 5.86×10-3/site per year and 5.02×10-3/site per year. Conclusion The present flu outbreak was possibly induced by long-term circulation of influenza A virus (H1 N1) in human population and swine herds in America. There was no evidence proving that influenza virus in China involved in the present outbreak.     

甲型H1N1流行性感冒病毒血凝素蛋白基因进化研究

Objective To determine the evolutionary rate and divergence time of influenza A virus HA gene isolated recently worldwide pandemic and explore the origin and its transmission. Methods A total of 344 HI sequences available in the GenBank (including 248 isolated from human, 84 from swine, 11 from avian, and 1 from ferret) and 7 isolated in Shanghai were collected. The nucleotide substitution rate and time to most recent common ancestor (tMRCA) was calculated using molecular clock theory and Bayesian Skyline Plot (BSP) based on Markov chain Monte Carlo. Then genetic phylogeny was constructed referring to posterior distribution. Results It was found that H1 sequences in the US from human, swine and avian were clustered significantly with swine H1 ones from Asia phylogenetieally (Cluster US). The second cluster (Cluster Eurasian Human) nearly consisted of human H1 sequences isolated in other regions. The third cluster (Cluster Eurasian Animal) consisted of swine and avian H1 sequences from China and Italy respectively. As for all the H1 sequences, the evolutionary rate was of 2.57×10-3substitutions/site per year averagely (95% Highest Posterior Density: 1.96×10-3-3.03×10-3/site per year). The estimated dates for tMRCA of human H1 in Europe and swine H1 in the mainland of China were the earliest, with the corresponding rates of 6.46×10-3/site per year and 0.97×10-3/site per year respectively. The tMRCAs of human and swine H1 sequences from the US were similar, with the rates of 5.86×10-3/site per year and 5.02×10-3/site per year. Conclusion The present flu outbreak was possibly induced by long-term circulation of influenza A virus (H1 N1) in human population and swine herds in America. There was no evidence proving that influenza virus in China involved in the present outbreak.     

甲型H1N1流行性感冒病毒血凝素蛋白基因进化研究

Objective To determine the evolutionary rate and divergence time of influenza A virus HA gene isolated recently worldwide pandemic and explore the origin and its transmission. Methods A total of 344 HI sequences available in the GenBank (including 248 isolated from human, 84 from swine, 11 from avian, and 1 from ferret) and 7 isolated in Shanghai were collected. The nucleotide substitution rate and time to most recent common ancestor (tMRCA) was calculated using molecular clock theory and Bayesian Skyline Plot (BSP) based on Markov chain Monte Carlo. Then genetic phylogeny was constructed referring to posterior distribution. Results It was found that H1 sequences in the US from human, swine and avian were clustered significantly with swine H1 ones from Asia phylogenetieally (Cluster US). The second cluster (Cluster Eurasian Human) nearly consisted of human H1 sequences isolated in other regions. The third cluster (Cluster Eurasian Animal) consisted of swine and avian H1 sequences from China and Italy respectively. As for all the H1 sequences, the evolutionary rate was of 2.57×10-3substitutions/site per year averagely (95% Highest Posterior Density: 1.96×10-3-3.03×10-3/site per year). The estimated dates for tMRCA of human H1 in Europe and swine H1 in the mainland of China were the earliest, with the corresponding rates of 6.46×10-3/site per year and 0.97×10-3/site per year respectively. The tMRCAs of human and swine H1 sequences from the US were similar, with the rates of 5.86×10-3/site per year and 5.02×10-3/site per year. Conclusion The present flu outbreak was possibly induced by long-term circulation of influenza A virus (H1 N1) in human population and swine herds in America. There was no evidence proving that influenza virus in China involved in the present outbreak.