牛冠状病毒S和HE蛋白研究进展

Research Progress on S and HE Proteins of Bovine Coronaviruses

牛冠状病毒(Bovine coronavirus,BCoV)是引起新生犊牛腹泻、牛的呼吸道感染和成年牛冬痢的一种病原,主要通过粪-口感染和呼吸道气溶胶传播。研究表明,BCoV在亚临床感染的成年牛体内可持续存在,这可能是BCoV在牛群中广泛存在且能长期循环的原因。因此,BCoV的流行会对集约化牛场造成巨大的经济损失,BCoV的防控形势极其严峻。BCoV S蛋白包含主要的抗原位点,可与宿主表面的唾液酸(SA)结合,且S蛋白参与病毒与宿主细胞的吸附和膜融合过程,能促进宿主产生有效的中和抗体。BCoV HE蛋白具有乙酰酯酶活性和血凝活性,能与S蛋白协同附着于细胞表面并启动感染。S和HE蛋白均在病毒的组织或宿主嗜性及毒力等方面发挥重要作用,这些作用也为进一步开展BCoV病原研究及后续疫苗和药物的研制提供参考。笔者重点阐述了BCoV S和HE蛋白的分子结构及功能,以及BCoV基于S和HE蛋白的受体识别作用(包括利用N-乙酰-9-O-乙酰神经氨酸为糖结合受体,利用人类白细胞抗原Ⅰ类分子为蛋白结合受体)。受体识别是冠状病毒感染和致病的重要决定因素,也是宿主免疫监视和人类干预策略最重要的靶标之一。因此,充分了解BCoV S和HE蛋白的结构功能和受体识别作用对于了解病毒的致病机制及抗病毒药物、疫苗的研发具有重要意义。

Bovine coronavirus(BCoV)is a pathogenic agent that causes diarrhoea in newborn calves,respiratory infections in cattle and winter dysentery in adult cattle,and is mainly transmitted by faecal-oral infection and respiratory aerosols.Studies have shown that BCoV can persist in subclinically infected adult cattle,which may explain the widespread presence of BCoV in herds and its ability to circulate over time.The prevention and control of Bovine coronavirus disease is extremely critical,as the occurrence of the disease can cause great economic losses to intensive cattle farms.The BCoV S protein contains major antigenic sites that bind to salivary acid(SA)on the host surface,and the S protein is involved in adsorption and membrane fusion between the virus and the host cells,which promotes the production of potent neutralising antibodies by the host.The BCoV HE protein has acetyl esterase activity and haemagglutination activity,and can synergise with the S protein to attach to the cell surface and initiate infection.Both S and HE proteins play important roles in the tissue or host tropism and virulence of the virus,and these roles also provide references for the further study of the pathogenesis of BCoV,and the subsequent development of vaccines and drugs.The author focuses on the molecular structure and function of the BCoV S and HE proteins,and the role of BCoV in receptor recognition based on the S and HE proteins(including the use of N-acetyl-9-O-acetylneuraminic acid as a sugar-binding receptor,and the use of human leukocyte antigen classⅠmolecules as a protein-binding receptor).Receptor recognition is an important determinant of Coronavirus infection and pathogenesis,and it is also one of the most important targets for host immune surveillance and human intervention strategies.Therefore,a full understanding of the structure-function and receptor recognition roles of the S and HE proteins is important for understanding the viral pathogenesis as well as for the development of antiviral drugs and vaccines.