Specific binding of human P[28] rotavirus VP8* protein to blood group ABH antigens on type 1 chains.

IF 5.5 1区 医学 Q1 MICROBIOLOGY
PLoS Pathogens Pub Date : 2025-07-21 eCollection Date: 2025-07-01 DOI:10.1371/journal.ppat.1013298
Yi Zheng, Xiaoman Sun, Yuting Li, Beibei Huang, Yang Chen, Han Zhou, Cuiyan Cao, Wengang Chai, Zhaojun Duan, Dandi Li, Jingyu Yan, Xinmiao Liang
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引用次数: 0

Abstract

Group A rotavirus (RV) has been the major cause of acute gastroenteritis in infants and young children. Among the five P genogroups almost all P genotype RVs in P[II], P[III] and P[IV] genogroups that infect humans can bind glycan histo-blood group antigens (HBGAs) as the receptors on the host cell surface to infect host through the viral spike protein VP8*. Although P[I] is the largest genogroup, P[28] and P[10] are the only two genotype RVs infecting humans in the group. It has recently been found that a P[28] strain is related to bat RV and considered a possible product of reassortment between bat and human RVs. Bats are increasingly being recognized as an important reservoir for viruses crossing species barriers to infect humans. Unrevealing the interactions between RVs and host receptors is important for understanding RV evolution, infection, and epidemic. In the present study, using a multiphasic approach, including X-ray crystallography, glycan microarray with a dedicated probe library, bio-layer interferometry, site-specific mutagenesis, and molecular docking and dynamics simulations, we found that P[28]-VP8* can bind to all blood group A, B and H(O) antigens but on type 1 chain only, without the capability to bind to any Lewis epitopes or mucin O-glycan cores. Different from most of the prevalent human RVs, such as P[8], P[4] and P[6], the broad HBGA binding specificity of P[28]-VP8* and the fact of the recently identified a possible reassortment P[28] strain of bat and human RVs have raised the concern of a future possibility of P[I] genogroup RV epidemic. RV surveillance may also need to take the P[I] genogroup RVs into account in the future.

人P[28]轮状病毒VP8*蛋白与1型链上血型ABH抗原的特异性结合
A组轮状病毒(RV)是婴幼儿急性胃肠炎的主要病因。在5个P基因群中,感染人类的P[II]、P[III]和P[IV]基因群中的P基因型rv几乎都能结合糖聚糖组织血型抗原(HBGAs)作为受体在宿主细胞表面通过病毒刺突蛋白VP8*感染宿主。虽然P[I]是最大的基因群,但P[28]和P[10]是该组中仅有的两种感染人类的基因型rv。最近发现一种p[28]毒株与蝙蝠RV有关,并被认为是蝙蝠和人类RV重新组合的可能产物。蝙蝠越来越被认为是病毒跨越物种屏障感染人类的重要宿主。揭示RV与宿主受体之间的相互作用对于理解RV的进化、感染和流行具有重要意义。在本研究中,我们使用多相方法,包括x射线晶体学、专用探针库的聚糖微阵列、生物层干涉法、位点特异性诱变、分子对接和动力学模拟,我们发现P[28]-VP8*可以结合所有血型a、B和H(O)抗原,但仅在1型链上,而不能结合任何刘易斯表位或粘蛋白O-聚糖核心。与大多数流行的人类RV,如P[8]、P[4]和P[6]不同,P[28]-VP8*具有广泛的HBGA结合特异性,以及最近发现的蝙蝠和人类RV可能重组的P[28]株,这引起了人们对P[I]基因组RV未来可能流行的关注。在未来,RV监测可能还需要考虑P[I]基因组RV。
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来源期刊
PLoS Pathogens
PLoS Pathogens MICROBIOLOGY-PARASITOLOGY
自引率
3.00%
发文量
598
期刊介绍: Bacteria, fungi, parasites, prions and viruses cause a plethora of diseases that have important medical, agricultural, and economic consequences. Moreover, the study of microbes continues to provide novel insights into such fundamental processes as the molecular basis of cellular and organismal function.
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