Yu Xing, Mishra Rahul, Holloway Gavan, von Itzstein Mark, Coulson Barbara S, Blanchard Helen
Institute for Glycomics, Griffith University Gold Coast Campus, Southport, QLD, 4222, Australia.
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, 3000, Australia.
Chembiochem. 2015 Oct 12;16(15):2176-81. doi: 10.1002/cbic.201500360. Epub 2015 Sep 3.
Rotavirus-cell binding is the essential first step in rotavirus infection. This binding is a major determinant of rotavirus tropism, as host cell invasion is necessary to initiate infection. Initial rotavirus-cell interactions are mediated by carbohydrate-recognizing domain VP8* of the rotavirus capsid spike protein VP4. Here, we report the first observation of significant structural rearrangement of VP8* from human and animal rotavirus strains upon glycan receptor binding. The structural adaptability of rotavirus VP8* delivers important insights into how human and animal rotaviruses utilize the wider range of cellular glycans identified as VP8* binding partners. Furthermore, our studies on rotaviruses with atypical genetic makeup provide information expected to be critical for understanding the mechanisms of animal rotavirus gene emergence in humans and support implementation of epidemiologic surveillance of animal reservoirs as well as future vaccination schemes.
轮状病毒与细胞的结合是轮状病毒感染必不可少的第一步。这种结合是轮状病毒嗜性的主要决定因素,因为宿主细胞入侵是启动感染所必需的。轮状病毒与细胞的初始相互作用由轮状病毒衣壳刺突蛋白VP4的碳水化合物识别结构域VP8介导。在此,我们首次观察到人类和动物轮状病毒株的VP8在与聚糖受体结合后发生显著的结构重排。轮状病毒VP8的结构适应性为人类和动物轮状病毒如何利用被鉴定为VP8结合伙伴的更广泛细胞聚糖提供了重要见解。此外,我们对具有非典型基因组成的轮状病毒的研究提供了预期对理解动物轮状病毒基因在人类中出现的机制至关重要的信息,并支持对动物宿主进行流行病学监测以及未来疫苗接种计划的实施。