Effect of the addition of oligosaccharides on the biological activities and antigenicity of influenza A/H3N2 virus hemagglutinin
Effect of the addition of oligosaccharides on the biological activities and antigenicity of influenza A/H3N2 virus hemagglutinin
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DOI：
10.1128/jvi.78.18.9605-9611.2004
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发表时间：
2004-09-01
影响因子：
5.4
通讯作者：
Hongo, S
中科院分区：
文献类型：
--
作者：
Abe, Y;Takashita, E;Hongo, S
自1968年出现以来，甲型H3 N2流感病毒在血凝素（RA）蛋白的球状头部上发展了越来越多的糖基化位点。本文研究了在A/H3 N2病毒HA中加入寡糖链对其生物学活性的影响。我们构建了7个突变体HA的A/爱知/2/68病毒与1至6个糖基化位点的球状头部，在自然分离物中发现，通过定点诱变，并分析了它们的细胞内转运，受体结合，和细胞融合活性。突变HA的糖基化位点对应于代表性A/H3 N2分离株（A/维多利亚/3/75、A/孟菲斯/6/86或A/悉尼/5/97）。结果表明，所有的突变HA被有效地运输到细胞表面的野生型HA。虽然突变HA含有3至6个糖基化位点的受体结合活性下降，其细胞融合活性不受影响。具有4 - 6个糖基化位点的突变HA与1976年收集的人血清的反应性远低于野生型HA。因此，向A/H3 N2病毒HA的球状头部添加新的寡糖可能使该病毒具有通过改变抗原性来逃避抗体压力的能力，而不会在生物活性方面产生不可接受的缺陷。
Influenza A/H3N2 viruses have developed an increased number of glycosylation sites on the globular head of the hemagglutinin (RA) protein since their appearance in 1968. Here, the effect of addition of oligosaccharide chains to the HA of A/H3N2 viruses on its biological activities was investigated. We constructed seven mutant HAs of A/Aichi/2/68 virus with one to six glycosylation sites on the globular head, as found in natural isolates, by site-directed mutagenesis and analyzed their intracellular transport, receptor binding, and cell fusion activities. The glycosylation sites of mutant HAs correspond to representative A/H3N2 isolates (A/Victoria/3/75, A/Memphis/6/86, or A/Sydney/5/97). The results showed that all the mutant HAs were transported to the cell surface as efficiently as wild-type HA. Although mutant HAs containing three to six glycosylation sites decreased receptor binding activity, their cell fusion activity was not affected. The reactivity of mutant HAs having four to six glycosylation sites with human sera collected in 1976 was much lower than that of wild-type HA. Thus, the addition of new oligosaccharides to the globular head of the HA of A/H3N2 viruses may have provided the virus with an ability to evade antibody pressures by changing antigenicity without an unacceptable defect in biological activity.