Muñoz-Alía Miguel Ángel, Fernández-Muñoz Rafael, Casasnovas José María, Porras-Mansilla Rebeca, Serrano-Pardo Ángela, Pagán Israel, Ordobás María, Ramírez Rosa, Celma María Luisa
Virology Unit and National Reference Laboratory for Measles, Ramón y Cajal Hospital, Madrid, Spain.
Virology Unit and National Reference Laboratory for Measles, Ramón y Cajal Hospital, Madrid, Spain.
Virus Res. 2015 Jan 22;196:122-7. doi: 10.1016/j.virusres.2014.11.015. Epub 2014 Nov 20.
Measles virus circulates endemically in African and Asian large urban populations, causing outbreaks worldwide in populations with up-to-95% immune protection. We studied the natural genetic variability of genotype B3.1 in a population with 95% vaccine coverage throughout an imported six month measles outbreak. From first pass viral isolates of 47 patients we performed direct sequencing of genomic cDNA. Whilst no variation from index case sequence occurred in the Nucleocapsid gene hyper-variable carboxy end, in the Hemagglutinin gene, main target for neutralizing antibodies, we observed gradual nucleotide divergence from index case along the outbreak (0% to 0.380%, average 0.138%) with the emergence of transient and persistent non-synonymous and synonymous mutations. Little or no variation was observed between the index and last outbreak cases in Phosphoprotein, Nucleocapsid, Matrix and Fusion genes. Most of the H non-synonymous mutations were mapped on the protein surface near antigenic and receptors binding sites. We estimated a MV-Hemagglutinin nucleotide substitution rate of 7.28 × 10-6 substitutions/site/day by a Bayesian phylogenetic analysis. The dN/dS analysis did not suggest significant immune or other selective pressures on the H gene during the outbreak. These results emphasize the usefulness of MV-H sequence analysis in measles epidemiological surveillance and elimination programs, and in detection of potentially emergence of measles virus neutralization-resistant mutants.
麻疹病毒在非洲和亚洲的大型城市人群中呈地方性流行，在免疫保护率高达95%的人群中引发全球范围的疫情。我们在一次持续六个月的输入性麻疹疫情中，对疫苗接种率达95%的人群中B3.1基因型的自然遗传变异性进行了研究。从47例患者的初代病毒分离株中，我们对基因组cDNA进行了直接测序。虽然在核衣壳基因高变羧基末端未出现与索引病例序列的变异，但在作为中和抗体主要靶点的血凝素基因中，我们观察到在疫情期间与索引病例的核苷酸逐渐发生分歧（0%至0.380%，平均0.138%），出现了瞬时和持续的非同义及同义突变。在磷蛋白、核衣壳、基质和融合基因中，索引病例与疫情末期病例之间几乎没有观察到变异。大多数血凝素非同义突变位于抗原和受体结合位点附近的蛋白表面。通过贝叶斯系统发育分析，我们估计麻疹病毒血凝素核苷酸替换率为7.28×10-6替换/位点/天。dN/dS分析并未表明疫情期间血凝素基因受到显著的免疫或其他选择压力。这些结果强调了麻疹病毒血凝素序列分析在麻疹流行病学监测和消除计划以及检测潜在的麻疹病毒中和抗性突变体出现方面的有用性。
