HOST CELL-MEDIATED VARIATION IN H3N2 INFLUENZA-VIRUSES
HOST CELL-MEDIATED VARIATION IN H3N2 INFLUENZA-VIRUSES
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DOI：
10.1016/0042-6822(87)90418-1
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发表时间：
1987-02-01
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;NAEVE, CW;WEBSTER, RG
研究了宿主细胞对甲型H3N2流感病毒抗原变异选择的影响以及宿主细胞选择与这些病毒诱导免疫的相关性。在一次流感流行期间，从人类临床样本中分离出流感病毒，在哺乳动物Madin-Darby犬肾（MDCK）细胞或胚胎鸡蛋中传代，并用一组单克隆抗体检测血凝素（HA）分子的抗原变异性。在许多情况下，在鸡蛋中培养的病毒的HA与在哺乳动物细胞中培养的同一个体的病毒的HA在抗原性上是不同的。从不同个体中回收的病毒在哺乳动物细胞系中培养时，在抗原性上彼此相似，但在卵中培养时，在抗原性上是异质的。从不同个体分离的HA基因序列分析表明，在流行病期间，彼此之间存在5或6个氨基酸残基的差异。从同一个体获得的MDCK细胞培养和蛋培养病毒的HA基因序列分析表明，MDCK细胞培养和蛋培养的A/Mem/12/85病毒抗原性不同的HA基因之间的分子变化涉及HA分子顶端紧邻受体结合位点的HA1残基156上的单个氨基酸替换。然而，从另一个个体分离的mdck生长病毒和鸡蛋生长病毒（A/Mem/2/85）的ha的氨基酸序列是相同的，尽管这些病毒在抗ha单克隆抗体检测时表现出抗原差异。因此，HA分子中单个氨基酸的变化可能不是MDCK细胞培养和卵培养病毒对间HA抗原变化的唯一原因，编码HA的基因以外的基因可能导致宿主细胞介导的这些病毒的抗原变异。然而，在鸡蛋和MDCK细胞中生长的病毒之间的抗原差异并不影响它们的保护能力，因为感染活鸡蛋生长的病毒或MDCK生长的病毒的雪貂同样受到保护，免受两种宿主细胞类型中生长的病毒的攻击。
The influence of the host cell on the selection of antigenic variants of influenza A H3N2 viruses and the relevance of host cell selection to the induction of immunity by these viruses have been investigated. Influenza viruses were isolated from human clinical samples during a single epidemic, were passaged in mammalian Madin-Darby Canine Kidney (MDCK) cells or in embryonated hens eggs, and were tested for antigenic variability in the hemagglutinin (HA) molecule with a panel of monoclonal antibodies. In many cases, the HA of virus cultivated in eggs was antigenically distinct from the HA of virus from the same individual grown in mammaian cells. Viruses recovered from different individuals were antigenically similar to each other when grown in mammalian cell lines yet were antigenically heterogeneous when cultivated in eggs. The HA genes of viruses isolated from different individuals during the epidemic were shown, by sequence analysis, to differ from each other by five or six amino residues. Sequence analysis of the HA genes of MDCK cell-grown and egg-grown virus obtained from the same individual demonstrated that the molecular changes between antigenically distinct HAs of MDCK cell- and egg-grown A/Mem/12/85 virus involved a single amino acid substitution at residue 156 in HA1, which lies at the tip of the HA molecule and immediately adjacent to the receptor-binding site. However, the amino acid sequences of HAs from MDCK-grown and egg-grown viruses (A/Mem/2/85) isolated from a second individual were identical although these viruses exhibited antigenic differences when examined with anti-HA monoclonal antibodies. Therefore, single amino acid changes in the HA molecule may not be the sole cause of antigen changes in the HA observed between pairs of MDCK cell-grown and egg-grown viruses and genes other than that encoding the HA may contribute to the host cell-mediated antigenic variation of these viruses. Nevertheless, antigenic differences between viruses grown in eggs and MDCK cells did not influence their ability to protect, since ferrets infected with either live egg-grown or MDCK-grown virus were protected equally well from challenge with virus grown in either host cell type.