Treanor J J, Snyder M H, London W T, Murphy B R
Laboratory of Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Virology. 1989 Jul;171(1):1-9. doi: 10.1016/0042-6822(89)90504-7.
The nonstructural (NS) genes of avian influenza A viruses have been divided into two groups on the basis of nucleotide sequence homology, which we have referred to here as alleles A and B. We sequenced the NS genes of eight additional avian influenza A viruses in order to define the differences between these two alleles more thoroughly. Four of the viruses had NS gene sequences which resembled that of A/FPV/Rostock/34 and belonged to allele A while the other four viruses had NS gene sequences more similar to that of A/Duck/Alberta/76 and belonged to allele B. There was approximately 90% sequence homology within alleles and 72% homology between alleles. As previously reported the NS genes of human influenza A viruses belong to allele A. We constructed single gene avian-human reassortant influenza A viruses containing an allele A or B NS gene segment from an avian influenza A virus and all other genes from a human influenza A virus and tested these reassortants for their ability to grow in the respiratory tract of a nonhuman primate. Reassortants containing an avian NS gene segment of allele B were significantly restricted in growth in the respiratory tract of squirrel monkeys while reassortants with an allele A NS gene segment were not. The divergent evolution of the B NS allele in birds may have resulted in gene products which do not function optimally in cooperation with genes from a human virus in viral replication in primate respiratory epithelium.
根据核苷酸序列同源性，甲型禽流感病毒的非结构（NS）基因已被分为两组，我们在此将其称为等位基因A和B。为了更全面地界定这两个等位基因之间的差异，我们对另外8种甲型禽流感病毒的NS基因进行了测序。其中4种病毒的NS基因序列与A/FPV/Rostock/34的相似，属于等位基因A，而另外4种病毒的NS基因序列与A/Duck/Alberta/76的更相似，属于等位基因B。等位基因内部的序列同源性约为90%，等位基因之间的同源性为72%。如先前报道，甲型人流感病毒的NS基因属于等位基因A。我们构建了单基因禽-人重配甲型流感病毒，其中包含来自甲型禽流感病毒的等位基因A或B的NS基因片段以及来自甲型人流感病毒的所有其他基因，并测试了这些重配病毒在非人灵长类动物呼吸道中的生长能力。含有等位基因B的禽NS基因片段的重配病毒在松鼠猴呼吸道中的生长受到显著限制，而含有等位基因A的NS基因片段的重配病毒则不受此影响。鸟类中B NS等位基因的趋异进化可能导致其基因产物在与人类病毒基因协同作用于灵长类呼吸道上皮细胞中的病毒复制时无法达到最佳功能。
