Antigenic and structural characterization of multiple subpopulations of H3N2 influenza virus from an individual.
Antigenic and structural characterization of multiple subpopulations of H3N2 influenza virus from an individual.
复制标题
个体 H3N2 流感病毒多个亚群的抗原和结构特征。
DOI：
10.1016/0042-6822(88)90588-0
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发表时间：
1988
期刊：
影响因子：
3.7
通讯作者：
Webster,RG
中科院分区：
文献类型：
--
作者：
Katz,JM;Webster,RG
与在哺乳动物细胞培养中培养的相同来源的流感病毒相比，在胚胎鸡蛋中培养的流感病毒通常具有抗原性可区分的血凝素(HA)。为了进一步调查病毒在个体之间的变异程度，从感染名为A/Mem/6/86(H3N2)的流感病毒期间48小时内收集的咽洗液中分离出病毒。从鸡卵和哺乳动物Madin-Darby犬肾(MDCK)细胞中分离到病毒，并对病毒的抗原性、结构和受体结合特性进行了测定。可以在MDCK细胞中分离到的病毒在原始样本中的出现频率是在鸡蛋中分离到的病毒的10到100倍。在MDCK细胞中分离的病毒克隆的血凝素在抗原性和结构上是相同的。相反，来自同一来源的病毒，在鸡蛋中以有限稀释选择，根据其HA分子的不同抗原性和结构特征，可以分为三个不同的亚群。不仅通过一组抗HA的单抗，而且还可以通过免疫雪貂血清和不同的蛋鸡克隆免疫血清来区分这三组鸡蛋生长病毒，以及它们与MDCK细胞生长病毒之间的区别。在这些组中，组1和组2分别代表了可在鸡蛋中分离到的一小部分病毒亚群，而第三种抗原表型的病毒在鸡蛋中分离最频繁。鸡蛋病毒血凝素中的氨基酸替换发生在分子的抗原和受体结合部位。第1组病毒的HA分子在HA1的第193和229位分别有两个氨基酸替换。与MDCK细胞培养的病毒和其他鸡蛋培养的病毒相比，第3组病毒的受体特异性发生了变化，在HA1的第145位有一个单一的氨基酸替代。与在MDCK细胞中分离的病毒相比，第2组鸡蛋培养病毒的HA在结构上看起来相同，但在抗原性和受体结合特性上显示出显著的差异。这些结果表明，在感染流感期间，可以从单个患者身上分离出多个不同的病毒亚群，并突显了为流行病学和疫苗目的选择最合适的病毒的潜在问题，因为选择可能导致使用不能代表在人类群体中占主导地位的病毒。
Influenza viruses grown in embryonated chicken eggs frequently possess antigenically distinguishable hemagglutinin (HA) compared to virus from the same source grown in mammalian cell culture. To further investigate the extent of variation among viruses from an individual, viruses were isolated from throat washes collected over a 48-hr period during infection with influenza virus designated A/Mem/6/86 (H3N2). Viruses were isolated from limit dilutions in eggs and mammalian Madin-Darby canine kidney (MDCK) cells and the antigenic, structural, and receptor-binding properties of these viruses were determined. Viruses which could be isolated in MDCK cells were present at 10- to 100-fold higher frequency in the original sample than viruses which could be isolated in eggs. The HA of virus clones isolated in MDCK cells were antigenically and structurally identical. In contrast, viruses from the same source, selected at limit dilution in eggs, could be divided into three distinct subpopulations based on the distinguishable antigenic and structural characteristics of their HA molecules. The three groups of egg-grown viruses could be distinguished from each other, and from MDCK cell-grown viruses, not only by a panel of anti-HA monoclonal antibodies, but also by immune ferret sera raised to H3N2 virus strains of recent years and sera raised to the different egg-grown clones themselves. Of these groups, group 1 and group 2 egg-grown viruses each represented a minor subpopulation of viruses which could be isolated in eggs, while viruses of the third antigenic phenotype were the most frequently isolated in eggs. Amino acid substitutions in the HA of egg-grown viruses occurred in antigenic and receptor-binding sites of the molecule. Group 1 viruses each possessed two amino acid substitutions in their HA molecules at residues 193 and 229 in HA1. Group 3 viruses, which displayed altered receptor specificities compared to MDCK cell-grown viruses and other egg-grown viruses, possessed a single amino acid substitution at residue 145 in HA1. The HA of the group 2 egg-grown viruses appeared structurally identical, yet displayed marked differences in antigenic and receptor-binding properties, compared to viruses isolated in MDCK cells. These results demonstrate that multiple, distinct subpopulations of virus can be isolated from a single patient during an infection with influenza and highlights the potential problems in selecting the most appropriate virus for epidemiological and vaccine purposes since selection could result in the use of viruses that are not representative of those which predominate in a human population.