Genetic characterization of EV71 isolates from 2004 to 2010 reveals predominance and persistent circulation of the newly proposed genotype D and recent emergence of a distinct lineage of subgenotype C2 in Hong Kong

Virology Journal

Kwok-Yung Yuen³  Patrick CY Woo³  Kwok-Hung Chan¹  Janice YC Lo²  Susanna KP Lau³  Cyril CY Yip¹ 

[1] Department of Microbiology, The University of Hong Kong, Hong Kong, China;Centre for Health Protection, Department of Health, Hong Kong, China;Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China

关键词: Hong Kong;    Epidemics;    Lineage;    Recombination;    Hand foot and mouth disease;    Enterovirus 71;   

Others  :  1149153
DOI  :  10.1186/1743-422X-10-222

 received in 2013-02-07, accepted in 2013-06-25,  发布年份 2013

【 摘 要 】

Background

Enterovirus 71 (EV71) is a common etiological agent of hand, foot and mouth disease (HFMD) in children. EV71 epidemics have been reported in Hong Kong in recent years, and yet the genetic information of EV71 strains circulating in our locality is limited. The objective of this study was to investigate the genetic evolution of these EV71 isolates in Hong Kong over a 7-year period.

Methods

Twenty-two EV71 isolates from Hong Kong during 2004–2010 were included for phylogenetic analysis using partial VP2-VP3, 2C and 3D regions. Eight EV71 strains were selected for complete genome sequencing and recombination analysis.

Results

Among the 22 EV71 isolates, 20 belonged to subgenotype C4 and 2 belonged to subgenotype C2 based on the phylogenetic analysis of partial VP2-VP3, 2C and 3D gene regions. Phylogenetic, similarity plot and bootscan analyses using complete genome sequences of seven EV71 isolates of subgenotype C4 supported that the “double-recombinant” strains of subgenotype C4 persistently circulating in Hong Kong should belong to a newly proposed genotype D. Further analysis revealed two clusters, subgenotypes C4b and C4a (proposed genotypes D1a and D1b respectively), with “genotype D1b” strains being predominant in recent years in Hong Kong. A distinct lineage of EV71 subgenotype C2 has emerged in Hong Kong in 2008. The evolutionary rate of EV71 was 3.1 × 10^-3 nucleotide substitutions per site per year similar to that of other enterovirus, such as EV68, but was relatively lower than those of echovirus 30 and poliovirus. Molecular clock analysis using VP1 gene dated the time to the most recent common ancestor of all EV71 genotypes to 1900s, while the EV71 “double-recombinant” strains of “genotype D” were detected as early as 1998.

Conclusions

This study provides the molecular basis for proposing a new “genotype D” of EV71 and assigning a discrete lineage of subgenotype C2. EV71 strains of “genotype D” have been circulating in Hong Kong for over 7 years, with “genotype D1b” being predominant.

【 授权许可】

   
2013 Yip et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Pallansch M, Roos R: Enteroviruses: polioviruses, coxsackieviruses, echoviruses and newer enteroviruses. In Fields Virology. 5th edition. Edited by Knipe DM, Howley PM. Philadelphia: Lippincoit Williams & Wilkins; 2007:840-893.
• [2]Wong SS, Yip CC, Lau SK, Yuen KY: Human enterovirus 71 and hand, foot and mouth disease. Epidemiol Infect 2010, 138:1071-1089.
• [3]Ho M: Enterovirus 71: the virus, its infections and outbreaks. J Microbiol Immunol Infect 2000, 33:205-216.
• [4]Cardosa MJ, Perera D, Brown BA, Cheon D, Chan HM, Chan KP, Cho H, McMinn P: Molecular epidemiology of human enterovirus 71 strains and recent outbreaks in the Asia-Pacific region: comparative analysis of the VP1 and VP4 genes. Emerg Infect Dis 2003, 9:461-468.
• [5]Schmidt NJ, Lennette EH, Ho HH: An apparently new enterovirus isolated from patients with disease of the central nervous system. J Infect Dis 1974, 129:304-309.
• [6]Brown BA, Pallansch MA: Complete nucleotide sequence of enterovirus 71 is distinct from poliovirus. Virus Res 1995, 39:195-205.
• [7]Yu H, Chen W, Chang H, Tang R, Zhao J, Gan L, Liu B, Chen J, Wang M: Genetic analysis of the VP1 region of enterovirus 71 reveals the emergence of genotype A in central China in 2008. Virus Genes 2010, 41:1-4.
• [8]Huang YP, Lin TL, Kuo CY, Lin MW, Yao CY, Liao HW, Hsu LC, Yang CF, Yang JY, Chen PJ, Wu HS: The circulation of subgenogroups B5 and C5 of enterovirus 71 in Taiwan from 2006 to 2007. Virus Res 2008, 137:206-212.
• [9]van der Sanden S, Koopmans M, Uslu G, van der Avoort H, Dutch Working Group for Clinical V: Epidemiology of enterovirus 71 in the Netherlands, 1963 to 2008. J Clin Microbiol 2009, 47:2826-2833.
• [10]Yip CC, Lau SK, Woo PC, Chan KH, Yuen KY: Complete genome sequence of a coxsackievirus A22 strain in Hong Kong reveals a natural intratypic recombination event. J Virol 2011, 85:12098-12099.
• [11]Lukashev AN, Lashkevich VA, Ivanova OE, Koroleva GA, Hinkkanen AE, Ilonen J: Recombination in circulating enteroviruses. J Virol 2003, 77:10423-10431.
• [12]Kirkegaard K, Baltimore D: The mechanism of RNA recombination in poliovirus. Cell 1986, 47:433-443.
• [13]Drake JW: Rates of spontaneous mutation among RNA viruses. Proc Natl Acad Sci USA 1993, 90:4171-4175.
• [14]Jarvis TC, Kirkegaard K: Poliovirus RNA recombination: mechanistic studies in the absence of selection. EMBO J 1992, 11:3135-3145.
• [15]Yip CC, Lau SK, Zhou B, Zhang MX, Tsoi HW, Chan KH, Chen XC, Woo PC, Yuen KY: Emergence of enterovirus 71 "double-recombinant" strains belonging to a novel genotype D originating from southern China: first evidence for combination of intratypic and intertypic recombination events in EV71. Arch Virol 2010, 155:1413-1424.
• [16]Wang HY, Tsao KC, Hsieh CH, Huang LM, Lin TY, Chen GW, Shih SR, Chang LY: Inferring nonneutral evolution from contrasting patterns of polymorphisms and divergences in different protein coding regions of enterovirus 71 circulating in Taiwan during 1998–2003. BMC Evol Biol 2010, 10:294. BioMed Central Full Text
• [17]Huang SW, Hsu YW, Smith DJ, Kiang D, Tsai HP, Lin KH, Wang SM, Liu CC, Su IJ, Wang JR: Reemergence of enterovirus 71 in 2008 in Taiwan: dynamics of genetic and antigenic evolution from 1998 to 2008. J Clin Microbiol 2009, 47:3653-3662.
• [18]Huang SC, Hsu YW, Wang HC, Huang SW, Kiang D, Tsai HP, Wang SM, Liu CC, Lin KH, Su IJ, Wang JR: Appearance of intratypic recombination of enterovirus 71 in Taiwan from 2002 to 2005. Virus Res 2008, 131:250-259.
• [19]Chan YF, Sam IC, AbuBakar S: Phylogenetic designation of enterovirus 71 genotypes and subgenotypes using complete genome sequences. Infect Genet Evol 2010, 10:404-412.
• [20]Chan YF, AbuBakar S: Phylogenetic evidence for inter-typic recombination in the emergence of human enterovirus 71 subgenotypes. BMC Microbiol 2006, 6:74. BioMed Central Full Text
• [21]Ma E, Chan KC, Cheng P, Wong C, Chuang SK: The enterovirus 71 epidemic in 2008–public health implications for Hong Kong. Int J Infect Dis 2010, 14:e775-e780.
• [22]Zhang Y, Wang J, Guo W, Wang H, Zhu S, Wang D, Bai R, Li X, Yan D, Wang H, Zhang Y, Zhu Z, Tan X, An H, Xu A, Xu W: Emergence and transmission pathways of rapidly evolving evolutionary branch C4a strains of human enterovirus 71 in the central plain of China. PLoS One 2011, 6:e27895.
• [23]McWilliam Leitch EC, Cabrerizo M, Cardosa J, Harvala H, Ivanova OE, Koike S, Kroes AC, Lukashev A, Perera D, Roivainen M, Susi P, Trallero G, Evans DJ, Simmonds P: The association of recombination events in the founding and emergence of subgenogroup evolutionary lineages of human enterovirus 71. J Virol 2012, 86:2676-2685.
• [24]Perera D, Shimizu H, Yoshida H, Van Tu P, Ishiko H, McMinn P, Cardosa MJ: A comparison of the VP1, VP2, and VP4 regions for molecular typing of human enteroviruses. J Med Virol 2010, 82:649-657.
• [25]Brown BA, Oberste MS, Alexander JP Jr, Kennett ML, Pallansch MA: Molecular epidemiology and evolution of enterovirus 71 strains isolated from 1970 to 1998. J Virol 1999, 73:9969-9975.
• [26]Woo PC, Lau SK, Yip CC, Huang Y, Tsoi HW, Chan KH, Yuen KY: Comparative analysis of 22 coronavirus HKU1 genomes reveals a novel genotype and evidence of natural recombination in coronavirus HKU1. J Virol 2006, 80:7136-7145.
• [27]Lau SK, Lee P, Tsang AK, Yip CC, Tse H, Lee RA, So LY, Lau YL, Chan KH, Woo PC, Yuen KY: Molecular epidemiology of human coronavirus OC43 reveals evolution of different genotypes over time and recent emergence of a novel genotype due to natural recombination. J Virol 2011, 85:11325-11337.
• [28]Deshpande JM, Nadkarni SS, Francis PP: Enterovirus 71 isolated from a case of acute flaccid paralysis in India represents a new genotype. Curr Sci 2003, 84:1350-1353.
• [29]Rao CD, Yergolkar P, Shankarappa KS: Antigenic diversity of enteroviruses associated with nonpolio acute flaccid paralysis, India, 2007–2009. Emerg Infect Dis 2012, 18:1833-1840.
• [30]Centre for Health Protection: EVSCAN (Week 1). [http://www.chp.gov.hk/files/pdf/ev_scan_wk1_2012.pdf webcite]
• [31]Guan D, van der Sanden S, Zeng H, Li W, Zheng H, Ma C, Su J, Liu Z, Guo X, Zhang X, Liu L, Koopmans M, Ke C: Population dynamics and genetic diversity of C4 strains of human enterovirus 71 in mainland China, 1998–2010. PLoS One 2012, 7:e44386.
• [32]Tu PV, Thao NT, Perera D, Huu TK, Tien NT, Thuong TC, How OM, Cardosa MJ, McMinn PC: Epidemiologic and virologic investigation of hand, foot, and mouth disease, southern Vietnam, 2005. Emerg Infect Dis 2007, 13:1733-1741.
• [33]Lin KH, Hwang KP, Ke GM, Wang CF, Ke LY, Hsu YT, Tung YC, Chu PY, Chen BH, Chen HL, Kao CL, Wang JR, Eng HL, Wang SY, Hsu LC, Chen HY: Evolution of EV71 genogroup in Taiwan from 1998 to 2005: an emerging of subgenogroup C4 of EV71. J Med Virol 2006, 78:254-262.
• [34]Jeong EJ, Lee JH, Kim MS, Bae GR, Jung C, Lee K, Choi SM, Kim DK, Lee DS, Kim WD, Jee YM, Cheong HK, Lee SH: Molecular characterization of enteroviruses detected in Gyeong-Ju and Po-Hang provinces of Korea in 2003. Arch Virol 2010, 155:1707-1712.
• [35]Iwai M, Masaki A, Hasegawa S, Obara M, Horimoto E, Nakamura K, Tanaka Y, Endo K, Tanaka K, Ueda J, Shiraki K, Kurata T, Takizawa T: Genetic changes of coxsackievirus A16 and enterovirus 71 isolated from hand, foot, and mouth disease patients in Toyama, Japan between 1981 and 2007. Jpn J Infect Dis 2009, 62:254-259.
• [36]Chatproedprai S, Theanboonlers A, Korkong S, Thongmee C, Wananukul S, Poovorawan Y: Clinical and molecular characterization of hand-foot-and-mouth disease in Thailand, 2008–2009. Jpn J Infect Dis 2010, 63:229-233.
• [37]Zhang Y, Tan XJ, Wang HY, Yan DM, Zhu SL, Wang DY, Ji F, Wang XJ, Gao YJ, Chen L, An HQ, Li DX, Wang SW, Xu AQ, Wang ZJ, Xu WB: An outbreak of hand, foot, and mouth disease associated with subgenotype C4 of human enterovirus 71 in Shandong, China. J Clin Virol 2009, 44:262-267.
• [38]McMinn P, Lindsay K, Perera D, Chan HM, Chan KP, Cardosa MJ: Phylogenetic analysis of enterovirus 71 strains isolated during linked epidemics in Malaysia, Singapore, and Western Australia. J Virol 2001, 75:7732-7738.
• [39]Ho M, Chen ER, Hsu KH, Twu SJ, Chen KT, Tsai SF, Wang JR, Shih SR: An epidemic of enterovirus 71 infection in Taiwan. Taiwan enterovirus epidemic working group. N Engl J Med 1999, 341:929-935.
• [40]Tao Z, Wang H, Xu A: Identification of a C2 subgenogroup strain of enterovirus 71 in a retrospective study in Shandong Province, China, from 1990 to 2010. J Clin Microbiol 2012, 50:1823-1824.
• [41]Oberste MS, Maher K, Kilpatrick DR, Pallansch MA: Molecular evolution of the human enteroviruses: correlation of serotype with VP1 sequence and application to picornavirus classification. J Virol 1999, 73:1941-1948.
• [42]Linsuwanon P, Puenpa J, Suwannakarn K, Auksornkitti V, Vichiwattana P, Korkong S, Theamboonlers A, Poovorawan Y: Molecular epidemiology and evolution of human enterovirus serotype 68 in Thailand, 2006–2011. PLoS One 2012, 7:e35190.
• [43]McWilliam Leitch EC, Bendig J, Cabrerizo M, Cardosa J, Hyypiä T, Ivanova OE, Kelly A, Kroes AC, Lukashev A, MacAdam A, McMinn P, Roivainen M, Trallero G, Evans DJ, Simmonds P: Transmission networks and population turnover of echovirus 30. J Virol 2009, 83:2109-2118.
• [44]Jorba J, Campagnoli R, De L, Kew O: Calibration of multiple poliovirus molecular clocks covering an extended evolutionary range. J Virol 2008, 82:4429-4440.
• [45]Tee KK, Lam TT, Chan YF, Bible JM, Kamarulzaman A, Tong CY, Takebe Y, Pybus OG: Evolutionary genetics of human enterovirus 71: origin, population dynamics, natural selection, and seasonal periodicity of the VP1 gene. J Virol 2010, 84:3339-3350.
• [46]Worobey M: A novel approach to detecting and measuring recombination: new insights into evolution in viruses, bacteria, and mitochondria. Mol Biol Evol 2001, 18:1425-1434.
• [47]Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S: MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 2011, 28:2731-2739.
• [48]Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG: Clustal W and Clustal X version 2.0. Bioinformatics 2007, 23:2947-2948.
• [49]Drummond AJ, Rambaut A: BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol Biol 2007, 7:214. BioMed Central Full Text
• [50]Keane TM, Creevey CJ, Pentony MM, Naughton TJ, Mclnerney JO: Assessment of methods for amino acid matrix selection and their use on empirical data shows that ad hoc assumptions for choice of matrix are not justified. BMC Evol Biol 2006, 6:29. BioMed Central Full Text