Binding of the hemagglutinin from human or equine influenza H3 viruses to the receptor is altered by substitutions at residue 193
Binding of the hemagglutinin from human or equine influenza H3 viruses to the receptor is altered by substitutions at residue 193
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DOI：
10.1007/s00705-003-0287-2
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发表时间：
2004-08-01
影响因子：
2.7
通讯作者：
van der Werf, S
中科院分区：
文献类型：
--
作者：
Medeiros, R;Naffakh, N;van der Werf, S
流感病毒的血凝素（HA）与唾液酸（SA）的相互作用对于宿主范围限制是重要的。大多数人类H3具有Ser 193，而禽类和马的H3通常分别具有Asn或Lys。为了研究残基193在SA识别中的作用，通过诱变在人H3和马H3内引入取代。在表达野生型或突变型HA的COS-1细胞上进行的血细胞吸附试验表明，在马H3的背景下，K193 S取代降低了其结合几种动物红细胞的能力。使用去唾液酸化然后α 2，3或α 2，6再唾液酸化的鸡红细胞，我们表明对于人和马H3 s，在位置193处用带正电荷的精氨酸或赖氨酸取代丝氨酸分别增加了与其优选受体SA α 2，6 Gal和SA α 2，3Gal的结合。此外，当与L194 I置换组合时，S193 R置换诱导人H3与NeuAcalpha 2，3Gal的结合。
Interactions of the hemagglutinin (HA) of influenza viruses with sialic acids (SA) are important for host range restriction. Most human H3s have a Ser193, while avian and equine H3s usually have an Asn or a Lys, respectively. To investigate the role of residue 193 in the recognition of SA, substitutions were introduced by mutagenesis within a human H3 and an equine H3. Hemadsorption assays performed on COS-1 cells expressing wt or mutated HAs, showed that a K193S substitution in the context of an equine H3 decreased its ability to bind several animal erythrocytes. Using de- and then alpha2,3 or alpha2,6 re-sialylated chicken erythrocytes we showed that for both human and equine H3s, substitution of a Serine by positively-charged Arginine or Lysine at position 193 increased binding to its preferred receptor, SAalpha2,6Gal and SAalpha2,3Gal, respectively. Moreover, when combined with the L194I substitution, the S193R substitution induced binding of the human H3 to NeuAcalpha2,3Gal.