EVOLUTION OF THE H3 INFLUENZA-VIRUS HEMAGGLUTININ FROM HUMAN AND NONHUMAN HOSTS
EVOLUTION OF THE H3 INFLUENZA-VIRUS HEMAGGLUTININ FROM HUMAN AND NONHUMAN HOSTS
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DOI：
10.1128/jvi.66.2.1129-1138.1992
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发表时间：
1992-02-01
影响因子：
5.4
通讯作者：
WEBSTER, RG
中科院分区：
文献类型：
--
作者：
BEAN, WJ;SCHELL, M;WEBSTER, RG
比较了40个H3亚型禽流感病毒血凝素基因和9个H4亚型禽流感病毒血凝素基因的核苷酸和氨基酸序列，并分析了它们之间的进化关系。根据这些关系，研究了不同宿主中病毒血凝素突变特征的差异，并研究了1968年人类大流行毒株祖先产生期间发生的RNA序列变化。定义了三个主要谱系：一个仅包含马病毒分离株;一个仅包含禽病毒分离株;一个包含禽、猪和人病毒分离株。1968年的人类大流行毒株源自一种与从亚洲鸭身上分离出的病毒最为相似的禽流感病毒，该病毒可能在1965年传播给人类。从那时起，人类病毒已经从这个祖先分化出来，每年积累约7.9个核苷酸和3.4个氨基酸取代。在禽-人转变时的假设祖先毒株的序列重建表明，在禽病毒毒株和人大流行毒株之间的转变期间，成熟血凝素分子中只有6个氨基酸发生了变化。所有这些变化都位于已知影响受体结合和抗原性的分子区域。与人类H3流感病毒株不同，马病毒分离株在其他物种中没有近亲，并且似乎比人类病毒株更早地与禽流感病毒分离。据估计，突变在马病毒谱系中以每年约3.1个核苷酸和0.8个氨基酸积累。分析中的四个猪病毒分离株似乎都是独立引入猪的，其中两个来自人类病毒，两个来自禽类病毒。哺乳动物和禽类谱系中编码和非编码突变的比较显示，禽类病毒中编码与总核苷酸变化的比率显著较低。此外，H3和H4血清型的禽类病毒谱系，但不是哺乳动物病毒谱系，在系统发育树的内部分支中的氨基酸序列比在末端分支中的氨基酸序列具有更大的保守性。禽流感病毒与1968年大流行毒株的祖先之间的氨基酸差异很少，禽流感病毒的表型稳定性很高，这表明与祖先毒株相似的毒株将继续在鸟类中传播，并可重新引入人类。
The nucleotide and amino acid sequences of 40 influenza virus hemagglutinin genes of the H3 serotype from mammalian and avian species and 9 genes of the H4 serotype were compared, and their evolutionary relationships were evaluated. From these relationships, the differences in the mutational characteristics of the viral hemagglutinin in different hosts were examined and the RNA sequence changes that occurred during the generation of the progenitor of the 1968 human pandemic strain were examined. Three major lineages were defined: one containing only equine virus isolates; one containing only avian virus isolates; and one containing avian, swine, and human virus isolates. The human pandemic strain of 1968 was derived from an avian virus most similar to those isolated from ducks in Asia, and the transfer of this virus to humans probably occurred in 1965. Since then, the human viruses have diverged from this progenitor, with the accumulation of approximately 7.9 nucleotide and 3.4 amino acid substitutions per year. Reconstruction of the sequence of the hypothetical ancestral strain at the avian-human transition indicated that only 6 amino acids in the mature hemagglutinin molecule were changed during the transition between an avian virus strain and a human pandemic strain. All of these changes are located in regions of the molecule known to affect receptor binding and antigenicity. Unlike the human H3 influenza virus strains, the equine virus isolates have no close relatives in other species and appear to have diverged from the avian viruses much earlier than did the human virus strains. Mutations were estimated to have accumulated in the equine virus lineage at approximately 3.1 nucleotides and 0.8 amino acids per year. Four swine virus isolates in the analysis each appeared to have been introduced into pigs independently, with two derived from human viruses and two from avian viruses. A comparison of the coding and noncoding mutations in the mammalian and avian lineages showed a significantly lower ratio of coding to total nucleotide changes in the avian viruses. Additionally, the avian virus lineages of both the H3 and H4 serotypes, but not the mammalian virus lineages, showed significantly greater conservation of amino acid sequence in the internal branches of the phylogenetic tree than in the terminal branches. The small number of amino acid differences between the avian viruses and the progenitor of the 1968 pandemic strain and the great phenotypic stability of the avian viruses suggest that strains similar to the progenitor strain will continue to circulate in birds and will be available for reintroduction into humans.