Glycans as receptors for influenza pathogenesis.
Glycans as receptors for influenza pathogenesis.
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聚糖作为流感发病机理的受体。
DOI：
10.1007/s10719-010-9303-4
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发表时间：
2010-08
影响因子：
3
通讯作者：
Sasisekharan, Ram
中科院分区：
文献类型：
--
作者：
Viswanathan, Karthik;Chandrasekaran, Aarthi;Srinivasan, Aravind;Raman, Rahul;Sasisekharan, V.;Sasisekharan, Ram
甲型流感病毒是正粘病毒科的成员，是每年季节性流感流行和偶尔全球大流行的原因。病毒外壳糖蛋白血凝素（HA）与宿主上皮细胞上的唾液酸化聚糖受体的结合是这些病毒感染和传播的关键初始步骤。科学家认为，HA结合特异性从Neu 5Ac α2-3Gal连接（α2-3）到Neu 5Ac α2- 6 Gal连接（α2-6）聚糖的转换对于病毒从禽类宿主到人类宿主的交叉至关重要。然而，研究表明，仅基于唾液酸键的HA聚糖结合偏好分类不足以建立HA的受体特异性与甲型流感病毒有效传播之间的相关性。最近的一项研究报告了人上呼吸道上皮中α2-6聚糖（超出唾液酸键）的结构和组成的广泛多样性，并确定了不同的聚糖结构拓扑。结合这些不同唾液酸化聚糖结构的多价HA的生物化学检查也表明，HA与具有特征性伞形结构拓扑的α2-6聚糖的高亲和力结合对于甲型流感病毒的有效人类适应和人-人传播至关重要。本文综述了唾液酸化聚糖受体的结构在流感病毒致病机制中的作用，并提出了一个新的研究范式。
Influenza A viruses, members of the Orthomyxoviridae family, are responsible for annual seasonal influenza epidemics and occasional global pandemics. The binding of viral coat glycoprotein hemagglutinin (HA) to sialylated glycan receptors on host epithelial cells is the critical initial step in the infection and transmission of these viruses. Scientists believe that a switch in the binding specificity of HA from Neu5Acα2-3Gal linked (α2-3) to Neu5Acα2-6Gal linked (α2-6) glycans is essential for the crossover of the viruses from avian to human hosts. However, studies have shown that the classification of glycan binding preference of HA based on sialic acid linkage alone is insufficient to establish a correlation between receptor specificity of HA and the efficient transmission of influenza A viruses. A recent study reported extensive diversity in the structure and composition of α2-6 glycans (which goes beyond the sialic acid linkage) in human upper respiratory epithelia and identified different glycan structural topologies. Biochemical examination of the multivalent HA binding to these diverse sialylated glycan structures also demonstrated that high affinity binding of HA to α2-6 glycans with a characteristic umbrella-like structural topology is critical for efficient human adaptation and human-human transmission of influenza A viruses. This review summarizes studies which suggest a new paradigm for understanding the role of the structure of sialylated glycan receptors in influenza virus pathogenesis.
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影响因子：
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作者：
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通讯作者：
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