Recent H3N2 Viruses Have Evolved Specificity for Extended, Branched Human-type Receptors, Conferring Potential for Increased Avidity.
Recent H3N2 Viruses Have Evolved Specificity for Extended, Branched Human-type Receptors, Conferring Potential for Increased Avidity.
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DOI：
10.1016/j.chom.2016.11.004
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发表时间：
2017-01-11
影响因子：
30.3
通讯作者：
Paulson JC
中科院分区：
文献类型：
--
作者：
Peng W;de Vries RP;Grant OC;Thompson AJ;McBride R;Tsogtbaatar B;Lee PS;Razi N;Wilson IA;Woods RJ;Paulson JC
人和禽流感病毒识别不同的含唾液酸受体，分别称为人型（NeuAc α 2 - 6Gal）和禽型（NeuAc α 2 - 3Gal）。这为禽流感病毒在人类和雪貂中的气溶胶液滴传播提供了物种屏障。最近的报告表明，目前的人类H3N2病毒不再对人类型受体具有严格的特异性。使用具有延伸的气道聚糖的流感受体聚糖微阵列，我们发现H3N2病毒实际上保持了人型特异性，但已经进化出对包含具有延伸的聚-N-乙酰基-乳糖胺（poly-LacNAc）链的支链聚糖的受体子集的偏好，这与2009年大流行性H1N1（Cal/04）血凝素共享特异性。延长的唾液酸苷受体的脂质连接形式可以恢复唾液酸酶处理的MDCK细胞对最近（A/维多利亚/361/11）和历史（A/香港/8/1968）H3N2病毒感染的易感性。值得注意的是，这些具有延长分支的人型受体具有通过同时结合单个血凝素三聚体的两个亚基来增加亲合力的潜力。
Human and avian influenza viruses recognize different sialic acid-containing receptors, referred to as human-type (NeuAcα2-6Gal) and avian-type (NeuAcα2-3Gal) respectively. This presents a species barrier for aerosol droplet transmission of avian viruses in humans and ferrets. Recent reports have suggested that current human H3N2 viruses no longer have strict specificity towards human-type receptors. Using an influenza receptor glycan microarray with extended airway glycans we find that H3N2 viruses have in fact maintained human-type specificity, but have evolved preference for a subset of receptors comprising branched glycans with extended poly-N-acetyl-lactosamine (poly-LacNAc) chains, a specificity shared with the 2009 pandemic H1N1 (Cal/04) hemagglutinin. Lipid-linked versions of extended sialoside receptors can restore susceptibility of sialidase-treated MDCK cells to infection by both recent (A/Victoria/361/11) and historical (A/Hong Kong/8/1968) H3N2 viruses. Remarkably, these human-type receptors with elongated branches have the potential to increase avidity by simultaneously binding to two subunits of a single hemagglutinin trimer.