Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Igua 4225, 11400 Montevideo, Uruguay.
Virus Res. 2012 Dec;170(1-2):91-101. doi: 10.1016/j.virusres.2012.09.002. Epub 2012 Sep 13.
The first influenza pandemic of this century was declared in April of 2009, with the emergence of a novel H1N1 influenza A virus strain (H1N1pdm). Understanding the evolution of H1N1pdm populations within the South American region is essential for studying global diversification, emergence, resistance and vaccine efficacy. In order to gain insight into these matters, we have performed a Bayesian coalescent Markov Chain Monte Carlo analysis of hemagglutinin (HA) and neuraminidase (NA) gene sequences of all available and comparable HA and NA sequences obtained from H1N1pdm IAV circulating in the South American region. High evolutionary rates and fast population growths characterize the population dynamics of H1N1pdm strains in this region of the world. A significant contribution of first codon position to the mean evolutionary rate was found for both genes studied, revealing a high contribution of non-synonymous substitutions to the mean substitution rate. In the 178days period covered by these studies, substitutions in all HA epitope regions can be observed. HA substitutions D239G/N and Q310H have been observed only in Brazilian patients. While substitution D239G/N is not particularly associated to a specific genetic lineage, all strains bearing substitution Q310H were assigned to clade 6, suggesting a founder effect. None of the substitutions found in the NA proteins of H1N1pdm strains isolated in South America appears sufficiently close to affect the drug binding pocket for the three NA inhibitor antivirals tested. A more detailed analysis of NA proteins revealed epitope differences among 2010 vaccine and H1N1pdm IAV strains circulating in the South American region.
本世纪的第一次流感大流行于 2009 年 4 月宣布，当时出现了一种新型 H1N1 甲型流感病毒株（H1N1pdm）。了解南美地区 H1N1pdm 人群的进化对于研究全球多样化、出现、耐药性和疫苗效力至关重要。为了深入了解这些问题，我们对 H1N1pdmIAV 在南美地区流行的所有可用且可比的 HA 和 NA 基因序列进行了贝叶斯聚合酶链式反应马尔可夫链蒙特卡罗分析。高进化率和快速的种群增长特征是该地区 H1N1pdm 菌株的种群动态特征。对于研究的两个基因，都发现第一个密码子位置对平均进化率有显著贡献，这表明非同义取代对平均取代率有很高的贡献。在这些研究涵盖的 178 天期间，可以观察到所有 HA 表位区域的取代。仅在巴西患者中观察到 HA 取代 D239G/N 和 Q310H。虽然取代 D239G/N 与特定遗传谱系没有特别相关，但所有携带取代 Q310H 的菌株均被分配到 6 组，提示存在创始效应。在从南美分离的 H1N1pdm 株的 NA 蛋白中发现的取代均未接近足以影响三种 NA 抑制剂抗病毒药物结合口袋的程度。对 NA 蛋白的更详细分析显示，在南美流行的 2010 年疫苗和 H1N1pdmIAV 株之间存在表位差异。
