GⅡ.23基因型诺如病毒P蛋白的寡糖结合特征
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摘要
诺如病毒(Noroviruses,NoVs)是导致人急性胃肠炎的最重要病原体之一,也是引起食源性疾病暴发的首要病原体。组织血型抗原(Histo-blood groups antigens,HBGAs)是NoVs的受体或宿主易感因子。已有研究表明HBGAs与NoVs的感染和流行高度相关。GⅡ.23是最近报道的NoVs新基因型。为了研究GⅡ.23与HBGAs的结合特征,表达纯化GⅡ.23基因型的P蛋白之后,通过唾液和寡糖结合实验研究其与HBGAs的结合特性,并通过同源结构模拟探索GⅡ.23 P蛋白与糖抗原潜在的对接分子机制,与已经解析的GⅡ.10的P蛋白与岩藻糖的复合物结构进行重叠。结果发现,GⅡ.23 P蛋白可以与B型唾液结合,但不结合A、O~+和O~-非分泌型唾液;P蛋白与H双糖抗原发生结合;分子模拟显示GⅡ.23 P蛋白具有与岩藻糖环结合的类似特征。本研究首次揭示了GⅡ.23 P蛋白与HBGAs受体的结合特征,为深入探索GⅡ.23基因型NoVs的进化、感染以及流行的具体机制提供了基础资料。
Noroviruses(NoVs) cause acute gastroenteritis and the primary pathogens inducing outbreaks of food-borne diseases. Histo-blood groups antigens(HBGAs) might be receptors or host susceptibility factors of NoVs. HBGAs have been shown to be closely associated with NoVs infection and prevalence. The G Ⅱ.23 genotype of NoVs was reported recently. To study the binding pattern between G Ⅱ.23 and HBGAs, the P protein of G Ⅱ.23 were expressed and purified, and the binding feature of P protein to HBGAs was investigated using saliva and glycan binding assays. Homology modeling of P protein was built. The superimposition structural analysis of P protein of G Ⅱ.10 in complex with fucose was undertaken to explore the possible docking structural basis of P protein of G Ⅱ.23 and fucose. The results showed that P protein of G Ⅱ.23 was bound to type B saliva, and not bound to A or O secretors or non-secretor saliva. P protein could bind to the antigens of H disaccharides antigens. Homology modeling indicated that P protein could bind to the antigens of H disaccharides using a potential glycan-binding site. The results suggested an interaction between P protein of G Ⅱ.23 with HBGAs.These findings offer a potential basis for elucidating the mechanism of the evolution, infection and epidemiology of the G Ⅱ genotype.
Noroviruses(NoVs) cause acute gastroenteritis and the primary pathogens inducing outbreaks of food-borne diseases. Histo-blood groups antigens(HBGAs) might be receptors or host susceptibility factors of NoVs. HBGAs have been shown to be closely associated with NoVs infection and prevalence. The G Ⅱ.23 genotype of NoVs was reported recently. To study the binding pattern between G Ⅱ.23 and HBGAs, the P protein of G Ⅱ.23 were expressed and purified, and the binding feature of P protein to HBGAs was investigated using saliva and glycan binding assays. Homology modeling of P protein was built. The superimposition structural analysis of P protein of G Ⅱ.10 in complex with fucose was undertaken to explore the possible docking structural basis of P protein of G Ⅱ.23 and fucose. The results showed that P protein of G Ⅱ.23 was bound to type B saliva, and not bound to A or O secretors or non-secretor saliva. P protein could bind to the antigens of H disaccharides antigens. Homology modeling indicated that P protein could bind to the antigens of H disaccharides using a potential glycan-binding site. The results suggested an interaction between P protein of G Ⅱ.23 with HBGAs.These findings offer a potential basis for elucidating the mechanism of the evolution, infection and epidemiology of the G Ⅱ genotype.
引文
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[12] Jin M,Zhou Y K,Xie H P,Fu J G,He Y Q,Zhang S,Jing H B,Kong X Y,Sun X M,Li H Y,Zhang Q,Li K, Zhang Y J, Zhou D Q, Xing W J, Liao Q H, Liu N,Yu H J, Jiang X,Tan M,Duan Z J. Characterization of the new GⅡ.17 norovirus variant that emerged recently as the predominant strain in China[J]. J Gen Virol, 2016, 97(10):2620-2632.
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[14] Tohma K, Lepore C J, Ford-Siltz L A,Parra G I. Evolutionary dynamics of non-GⅡgenotype 4(GⅡ.4)noroviruses reveal limited and independent diversification of variants[J].J Gen Virol, 2018, 99(8):1027-1035.
[15] Tohma K,Saito M, Mayta H, Zimic M, Lepore C J,Ford-Siltz L A,Gilman R H,Parra G I. Complete genome sequence of a nontypeable GⅡnorovirus detected in Peru[J/OL]. Genome Announc, 2018,6(10). pii:e00095-18.
[16] Hansman G S, Biertiimpfel C, Georgiev I,McLellan J S, Chen L, Zhou T, Katayama K, Kwong P D. Crystal structures of GⅡ. 10 and GⅡ.12 norovirus protruding domains in complex with histo-blood group antigens reveal details for a potential site of vulnerability[J]. J Virol, 2011, 85(13):6687-6701.
[17]Koromyslova A D,Leuthold M M,Bowler M W,Hansman G S. The sweet quartet:Binding of fucose to the norovirus capsid[J]. Virology, 2015, 483:203-208.
[2] Pietsch C, Ennuschat N, Hartel S, Liebert U G. Within-host evolution of virus variants during chronic infection with novel GⅡ.P26-GⅡ.26 norovirus[J]. J Clin Virol,2018, 108:96-102.
[3] Bok K,Abente E J,Realpe-Quintero M,Mitra T,Sosnovtsev S V, Kapikian A Z, Green K Y. Evolutionary dynamics of GⅡ.4 noroviruses over a 34-year period[J].J Virol, 2009, 83(22):11890-11901.
[4] Bull R A, White P A. Mechanisms of GⅡ.4 norovirus evolution[J]. Trends Microbiol, 2011, 19(5):233-240.
[5] Van Beek J,Ambert-Balay K,Botteldoorn N, Eden J S,Fonager J,Hewitt J,Iritani N,Kroneman A,Vennema H, Vinje J, White P A, Koopmans M; NoroNet. Indications for worldwide increased norovirus ac-tivity associated with emergence of a new variant of genotypeⅡ.4, late 2012[J]. Euro Surveill, 2013, 18(1):8-9.
[6] Tan M, Jiang X. Histo-blood group antigens:a common niche for norovirus and rotavirus[J/OL]. Expert Rev Mol Med, 2014, 16:e5.
[7] Lindesmith L C, Donaldson E F, Lobue A D,Cannon J L, Zheng D P, Vinje J, Baric R S. Mechanisms of GⅡ.4 norovirus persistence in human populations[J/OL].PLoS Med,2008, 5(2):e31.
[8] Tan M, Jiang X. The p domain of norovirus capsid protein forms a subviral particle that binds to histo-blood group antigen receptors[J]. J Virol, 2005, 79(22):14017-14030.
[9] Liu W,Chen Y,Jiang X,Xia M,Yang Y,Tan M,Li X,Rao Z.A unique human norovirus lineage with a distinct HBGA binding interface[J/OL]. PLoS Pathog,2015, 11(7):e1005025.
[10] Boon D, Mahar J E, Abente E J, Kirkwood C D, Purcell R H,Kapikian A Z,Green K Y,Bok K. Comparative evolution of GⅡ.3 and GⅡ.4 norovirus over a 31-year period[J]. J Virol, 2011, 85(17):8656-8666.
[11] Chan M C, Lee N, Hung T N, Kwok K, Cheung K,Tin E K, Lai R W, Nelson E A, Leung T F, Chan P K. Rapid emergence and predominance of a broadly recognizing and fast-evolving norovirus GⅡ.17 variant in late 2014[J]. Nat Commun, 2015, 6:10061.
[12] Jin M,Zhou Y K,Xie H P,Fu J G,He Y Q,Zhang S,Jing H B,Kong X Y,Sun X M,Li H Y,Zhang Q,Li K, Zhang Y J, Zhou D Q, Xing W J, Liao Q H, Liu N,Yu H J, Jiang X,Tan M,Duan Z J. Characterization of the new GⅡ.17 norovirus variant that emerged recently as the predominant strain in China[J]. J Gen Virol, 2016, 97(10):2620-2632.
[13] Parra G I,Squires R B,Karangwa C K, Johnson J A,Lepore C J,Sosnovtsev S V,Green K Y. Static and Evolving norovirus genotypes:implications for epidemiology and immunity[J/OL]. PLoS Pathog,2017,13(1):e1006136.
[14] Tohma K, Lepore C J, Ford-Siltz L A,Parra G I. Evolutionary dynamics of non-GⅡgenotype 4(GⅡ.4)noroviruses reveal limited and independent diversification of variants[J].J Gen Virol, 2018, 99(8):1027-1035.
[15] Tohma K,Saito M, Mayta H, Zimic M, Lepore C J,Ford-Siltz L A,Gilman R H,Parra G I. Complete genome sequence of a nontypeable GⅡnorovirus detected in Peru[J/OL]. Genome Announc, 2018,6(10). pii:e00095-18.
[16] Hansman G S, Biertiimpfel C, Georgiev I,McLellan J S, Chen L, Zhou T, Katayama K, Kwong P D. Crystal structures of GⅡ. 10 and GⅡ.12 norovirus protruding domains in complex with histo-blood group antigens reveal details for a potential site of vulnerability[J]. J Virol, 2011, 85(13):6687-6701.
[17]Koromyslova A D,Leuthold M M,Bowler M W,Hansman G S. The sweet quartet:Binding of fucose to the norovirus capsid[J]. Virology, 2015, 483:203-208.