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基于全基因组序列对一株来自印度西部浦那地区新生儿的罕见 A 组轮状病毒 G12P[11]进行的序列和结构特征分析。

Full genome based sequence and structural characterization of an unusual group A rotavirus G12P[11] isolated from neonates in Pune, western India.

机构信息

Enteric Viruses Group, ICMR-National Institute of Virology, Pune, India.

Bioinformatics and Data Management, ICMR-National Institute of Virology, Pune, India.

出版信息

Vaccine. 2020 Feb 28;38(10):2275-2291. doi: 10.1016/j.vaccine.2020.01.081. Epub 2020 Feb 3.

Abstract

Studies conducted at neonatal intensive care units in Pune, western India, suggested early exposure to rotaviruses and predominance of unusual human-bovine-like G12P[11] strains. The whole genome sequencing and phylogenetic analyses of a naturally attenuated, culture adapted neonatal strain, (NIV-1740121) revealed multiple-gene reassortment events, containing ROTAVAC® vaccine strain, 116E-like VP4, VP6, NSP3, NSP5 genes, VP7 gene of G12 origin and VP3 gene of porcine ancestry in a human Wa-like backbone. Analysis of 3D structure modeling of the VP7 and VP4 proteins with respect to 116E suggested amino acid variations in the major neutralizing epitopes of VP7, contributed to a modified charge density. Visualization of receptor-glycan interaction structures of NIV-1740121 and 116E VP8* showed type I glycan binds with a similar conformation at the same active site as represented in the available crystal structure of G10P[11] VP8*. The study adds to the knowledge of age restricted tropism of P[11] strains in neonates.

摘要

在印度西部浦那的新生儿重症监护病房进行的研究表明,轮状病毒的早期暴露和不常见的人-牛样 G12P[11]株的优势。对自然减毒、培养适应的新生株(NIV-1740121)进行全基因组测序和系统进化分析,发现了多个基因重配事件,包含 ROTAVAC®疫苗株、116E 样 VP4、VP6、NSP3、NSP5 基因、G12 来源的 VP7 基因和猪源 VP3 基因在人 Wa 样骨架中。对 VP7 和 VP4 蛋白的 3D 结构建模进行分析,发现 116E 与 VP7 的主要中和表位的氨基酸变异导致了电荷密度的改变。对 NIV-1740121 和 116E VP8的受体-聚糖相互作用结构的可视化显示,I 型聚糖以与可用的 G10P[11] VP8晶体结构中相同的活性位点相同的构象结合。该研究增加了对新生儿中 P[11]株的年龄限制嗜性的认识。

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