Zhang Xueyang, Shi Jinping, Ye Xiaohua, Ku Zhiqiang, Zhang Chao, Liu Qingwei, Huang Zhong
Unit of Vaccinology &Antiviral Strategies, CAS Key Laboratory of Molecular Virology &Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
Emerg Microbes Infect. 2017 Jul 26;6(7):e65. doi: 10.1038/emi.2017.55.
Coxsackievirus A16 (CVA16) is one of the major pathogens responsible for hand, foot and mouth disease, which affects more than two million children in the Asian-Pacific region annually. Previous studies have shown that scavenger receptor B2 is a functional receptor for CVA16 that facilitates the uncoating process. However, it remains unclear whether other receptors are required for efficient CVA16 infection. In this study, by using a variety of assays we demonstrated that CVA16 utilizes surface heparan sulfate glycosaminoglycans as its attachment receptor. We further showed that five surface-exposed positively charged residues located in a cluster at the five-fold vertex of the virion are critical to heparan sulfate binding and cellular attachment of CVA16. Among the five residues, the arginine at position 166 (R166) of VP1 capsid protein appeared to be the most important for the interaction between CVA16 and heparan sulfate. Alanine substitution at this site (R166A) almost completely abolished heparan sulfate binding and cellular attachment of the virus. Our work achieves insight into the early events of CVA16 infection, thereby providing information that may facilitate the rational design of antiviral drugs and vaccines against CVA16 infection.
柯萨奇病毒A16型（CVA16）是导致手足口病的主要病原体之一，该疾病每年在亚太地区影响超过200万儿童。先前的研究表明，清道夫受体B2是CVA16的功能性受体，可促进脱壳过程。然而，目前尚不清楚高效的CVA16感染是否还需要其他受体。在本研究中，我们通过多种实验证明，CVA16利用表面硫酸乙酰肝素糖胺聚糖作为其附着受体。我们进一步表明，位于病毒粒子五重顶点簇中的五个表面暴露的带正电荷残基对于CVA16与硫酸乙酰肝素的结合及细胞附着至关重要。在这五个残基中，衣壳蛋白VP1第166位的精氨酸（R166）似乎对CVA16与硫酸乙酰肝素之间的相互作用最为重要。该位点的丙氨酸替代（R166A）几乎完全消除了病毒与硫酸乙酰肝素的结合及细胞附着。我们的工作深入了解了CVA16感染的早期事件，从而提供了可能有助于合理设计抗CVA16感染的抗病毒药物和疫苗的信息。
