病毒病所發現同一型別人源和豬源輪狀病毒具有不同的受體結合特徵

導 讀

輪狀病毒（Rotavirus，RV）是引起急性胃腸炎的重要病原，但對於在人群中廣泛流行的輪狀病毒VP8*蛋白的受體類型及其結構基礎尚不明確。近日，中國疾病預防控制中心病毒病預防控制所段招軍研究員在A組P[6]和P[19]型輪狀病毒受體結合特徵方面取得重要進展，通過對豬源，豬相似的人源，以及人群中廣泛流行的毒株受體結合特徵的研究，發現同一型別不同來源的毒株可能具有不同的受體結合特徵，為研究輪狀病毒跨物種傳播分子機制奠定了基礎。相關研究成果以「GlycanBinding Specificity and Mechanism of Human and Porcine P[6]/P[19] Rotavirus VP8*s」為題，發表在國際病毒學專業期刊《Journal of Virology》上。

研究背景

輪狀病毒（Rotavirus，RV）是引起急性胃腸炎的重要病原。近來研究發現組織血型抗原（histo-bloodgroup antigens, HBGAs）、黏蛋白核心（mucin core）等糖可以與輪狀病毒VP8*蛋白相互作用。人群中廣泛流行的輪狀病毒型別有P[4]、P[6]、P[8]型，P[19]型輪狀病毒來源於豬，偶發性感染人。VP8*序列分析顯示P[6]、P[19]型輪狀病毒與P[4]和P[8]同屬於第二基因群組。對於這些輪狀病毒VP8*蛋白的受體類型及其結構基礎尚不明確。

結果速覽

1.本研究通過糖點陣，寡糖結合，唾液結合等實驗方法探索人和豬P[6]和P[19]型輪狀病毒VP8*蛋白的寡糖結合特徵（圖1）。結果發現：糖點陣研究發現人源（豬類似的人源）和豬源P[6]和P[19] VP8*蛋白與黏蛋白核心和1型組織血型抗原結合。寡糖結合實驗發現人和豬P[19]、豬P[6]、人P[4]、P[8]VP8*與黏蛋白核心2（mucincore 2）和1型組織血型抗原前體（Lactose-N-tetrarose，LNT）結合，人流行株P[6]與黏蛋白核心不結合而與1型組織血型抗原結合。這些結果提示，同一型別不同來源的毒株可能具有不同的受體結合特徵。

圖1 P[6]和P[19]與mucin core 2和LNT（lactose-N-tetrarose）寡糖結合實驗

2.利用晶體學方法解析了P[6] VP8*蛋白的結構（圖2），發現P[6] VP8*蛋白與P[19]VP8*結構最為相近。進一步解析了P[19] VP8*與mucincore 2及LNT的複合物結構，發現P[19]輪狀病毒具有與其他型別不同的受體結合位點。通過序列分析和結構比較發現該受體結合位點在P[6]、P[4]、P[8]VP8*中是保守的，提示P[6]、P[4]、P[8]VP8*也可能通過此位點與受體互作。

圖2 不同P型輪狀病毒VP8*受體結合位點比較及氨基酸序列比對

結 語

ABSTRACT

Rotaviruses (RVs), whichcause severe gastroenteritis in infants and children, recognize glycan ligandsin a genotype-dependent manner via the distal VP8* head of the spike proteinVP4. However, the glycan binding mechanisms remain elusive for the P[II]genogroup RVs, including the widely prevalent human RVs (P[8], P[4], and P[6]) and a rare P[19] RV. In this study, we characterized the glycan binding specificity of human and porcine P[6]/P[19] RV VP8* and found that the P[II] genogroup RV VP8*s could commonly interact with mucin core 2 which may play animportant role in the RV evolution and cross-species transmission. We determined the first P[6] VP8* structure, as well as the complex structures of human P[19] VP8* with core 2 and lacto-N-tetraose (LNT). A glycan binding site was identified in human P[19] VP8*. Structural super imposition and sequence alignment revealed the conservation of the glycan binding site in the P[II] genogroup RV VP8*s. Our data provide significant insight into the glycan binding specificity and glycan binding mechanism of the P[II] genogroup RVVP8*s, which would help understanding of RV evolution, transmission, epidemiology, and vaccine approach.

IMPORTANCE

Rotaviruses (RVs), belonging to the familyReoviridae, are double-stranded RNA viruses causing acute gastroenteritis in children and animals worldwide. Depending on phylogeny of the VP8* sequences, P[6] and P[19] RVs are grouped into the genogroup II together with P[4] and P[8] that are widely prevalent in humans.In this study, we characterized the glycan binding specificity of human and porcine P[6]/P[19] RV VP8*s, determined the crystal structure of P[6] VP8*, and uncovered the glycan binding pattern in P[19] VP8*, revealing a conservedglycan binding site in the VP8*s of P[II] genogroup RVs by structural superimposition and sequence alignment. Our data suggested that mucin core 2 may play an important role in the P[II] RV evolution and cross-species transmission. These data provide insight into cell attachment, infection, epidemiology, and evolution of P[II] genogroup RVs, which would help to developcontrol and prevention strategies against RVs.

參考文獻：

1.Xiaoman Sun, Dandi Li, Jianxun Qi， Wengang Chai, Luyao Wang, Lihong Wang,Ruchao Peng, Han Wang, Qing Zhang, Lili Pang, Xiangyu Kong, Hong Wang, MiaoJin, George F. Gao and Zhaojun Duan*.Glycan Binding Specificity and Mechanism of Human and Porcine P[6]/P[19] Rotavirus VP8*s.Journal of Virology.

doi: 10.1128/JVI.00538-18

本期編輯：Annabella

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