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Title of Journal: Virus Genes

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Abbravation: Virus Genes

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Springer US

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DOI

10.1007/978-3-319-12583-1_14

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1572-994X

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A novel finding for enterovirus virulence from the

Authors: Yongjuan Liu Chong Fu Suying Wu Xiong Chen Yingying Shi Bingfei Zhou Lianglu Zhang Fengfeng Zhang Zhihao Wang Yingying Zhang Chengpeng Fan Song Han Jun Yin Biwen Peng Wanhong Liu Xiaohua He
Publish Date: 2014/01/19
Volume: 48, Issue: 2, Pages: 260-272
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Abstract

Enterovirus 71 EV71 is a neurotropic virus that causes various clinical manifestations in young children ranging from asymptomatic to fatal Different pathotypes of EV71 notably differ in virulence Several virulence determinants of EV71 have been predicted However these reported virulence determinants could not be used to identify the EV71 strains of subgenotype C4 which mainly circulate in China In this study VP1 sequences of 37 EV71 strains from severe cases SCEV71 and 192 EV71 strains from mild cases MCEV71 in mainland China were analyzed to determine the potential virulence determinants in the capsid protein VP1 of EV71 Although most SCEV71 strains belonged to subgenotype C4a no specific genetic lineages in C4a were correlated with EV71 virulence Interestingly amino acid substitutions at nine positions H22Q P27S N31S/D E98K E145G/Q D164E T240A/S V249I and A289T were detected by aligning the VP1 sequences of the SCEV71 and MCEV71 strains Moreover both the constituent ratios of the conservative or mutated residues in the MCEV71 and SCEV71 strains and the changes in the VP1 3D structure resulting from these mutations confirmed that the conservative residues 22H 249V and 289A and the mutated residues 27S 31S/D 98K 145G/Q 164E and 240A/S might be potential virulence determinants in VP1 of EV71 Furthermore these results led to the hypothesis that VP1 acts as a sandwich switch for viral particle stabilization and cellular receptors attachment and specific mutations in this protein can convert mild cases into severe cases These findings highlight new opportunities for diagnostic and therapeutic interventionsWe are grateful to all the staffs engaged in investigating the epidemiology and pathogenicity of EV71 for their enormous contributions We especially thank the researchers for their achievement in the viral structure This work was supported by the National Natural Sciences Foundation of China Nos 81171577 81371790 81371422 and 81171127 the National Basic Research Program of China 2010CB529803 the National Science and Technology Major Projects of New Drugs 2012ZX09103301028 and the Fundamental Research Funds for the Central Universities of China Nos 201130102020001 201130102020002 and 2012301020207

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