Balanced hemagglutinin and neuraminidase activities are critical for efficient replication of influenza A virus
Balanced hemagglutinin and neuraminidase activities are critical for efficient replication of influenza A virus
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DOI：
10.1128/jvi.74.13.6015-6020.2000
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发表时间：
2000-07-01
影响因子：
5.4
通讯作者：
Kawaoka, Y
中科院分区：
文献类型：
--
作者：
Mitnaul, LJ;Matrosovich, MN;Kawaoka, Y
流感病毒A/WSN/33（WSN）的SD 0突变体，其特征在于在神经氨酸酶（NA）柄中缺失24个氨基酸，由于NA功能缺陷，不能在含胚鸡蛋中生长。SDO在卵中连续传代产生了10个高效复制的独立克隆。对这些卵适应病毒的表征表明，其中5种病毒在连接跨膜和催化头部结构域的区域中含有来自PB 1、PB 2或NP基因的NA基因插入，表明流感病毒RNA片段的重组相对频繁地发生。其他五种病毒在该区域不含插入，但与亲本病毒的结合特性相比，对唾液酸糖缀合物的结合亲和力降低。后者的病毒之一的序列分析显示，在血凝素（HA）基因的突变，在接近唾液酸受体结合口袋的网站。这些突变似乎补偿了由于茎缺失而降低的NA功能。因此，平衡的HA-NA功能对于有效的流感病毒复制是必需的。
The SD0 mutant of influenza virus A/WSN/33 (WSN), characterized by a 24-amino-acid deletion in the neuraminidase (NA) stalk, does not grow in embryonated chicken eggs because of defective NA function. Continuous passage of SDO in eggs yielded 10 independent clones that replicated efficiently. Characterization of these egg-adapted viruses showed that five of the viruses contained insertions in the NA gene from the PB1, PB2, or NP gene, in the region Linking the transmembrane and catalytic head domains, demonstrating that recombination of influenza viral RNA segments occurs relatively frequently. The other five viruses did not contain insertions in this region but displayed decreased binding affinity toward sialylglycoconjugates, compared with the binding properties of the parental virus. Sequence analysis of one of the latter viruses revealed mutations in the hemagglutinin (HA) gene, at sites in close proximity to the sialic acid receptor-binding pocket. These mutations appear to compensate for reduced NA function due to stalk deletions. Thus, balanced HA-NA functions are necessary for efficient influenza virus replication.