Changes in the hemagglutinin molecule of influenza type A (H3N2) virus associated with increased virulence for mice
Changes in the hemagglutinin molecule of influenza type A (H3N2) virus associated with increased virulence for mice
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DOI：
10.1007/s007050050060
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发表时间：
1997-01-01
影响因子：
2.7
通讯作者：
Anders, EM
中科院分区：
文献类型：
--
作者：
Hartley, CA;Reading, PC;Anders, EM
利用H3N2流感病毒A/Philippines/82 (Phil82)及其牛血清抗性突变体Phil82/BS研究影响流感病毒对小鼠毒力的因素。 Phil82/BS 在血凝素 (HA) 分子残基 165 处缺乏高甘露糖寡糖，被发现在小鼠肺中复制的滴度比亲本 Phil82 高得多，并且对小鼠具有致死性。 Phil82/BS 通过在小鼠中连续肺传代进一步适应，产生了毒力更大的菌株 Phil82/BS/ML10，其中 HA 残基 246 的变化导致第二个潜在糖基化位点的丢失。 Phil82 对鼠血清和肺相关甘露糖结合凝集素（collectins）的体外中和高度敏感。两种突变病毒的表征表明，对鼠集合素的抗性可以解释 Phi182/BS 毒力的增强，但不能解释 Phil82/BS/ML10 毒力的进一步增加。有证据表明，Phil82/BS HA 中的残基 246 实际上并未被糖基化，在亲本 Phil82 病毒中也可能未被糖基化。 Phil82/BS/ML10 的 HA 分子显示出与 Phil82/BS 的功能差异，包括融合的最佳 pH 值的变化和受体结合特异性的微小变化，这可能会提高小鼠肺中的复制效率。
The H3N2 influenza virus A/Philippines/82 (Phil82) and its bovine serum-resistant mutant, Phil82/BS, were used to investigate factors that influence virulence of influenza virus for mice. Phil82/BS, which lacks the high-mannose oligosaccharide at residue 165 of the hemagglutinin (HA) molecule, was found to replicate to a much higher titer in mouse lung than the parent Phil82, and had acquired lethality for mice. Further adaptation of Phil82/BS by sequential lung passage in mice yielded a strain of greater virulence, Phil82/BS/ML10, in which a change at residue 246 of HA resulted in loss of a second potential glycosylation site. Phil82 is highly sensitive to neutralization in vitro by murine serum- and lung-associated mannose-binding lectins (collectins). Characterization of the two mutant viruses indicated that resistance to murine collectins can account for the enhanced virulence of Phi182/BS but not for the further increase in virulence of Phil82/BS/ML10. Evidence is presented that residue 246 is not in fact glycosylated in Phil82/BS HA, nor presumably in the parent Phil82 virus. The HA molecule of Phil82/BS/ML10 displayed functional differences from Phil82/BS, including a change in the optimum pH of fusion and a minor change in receptor-binding specificity, which may allow improved efficiency of replication in the mouse lung.