Archives of Virology

, 156:2007

Molecular characterization and complete genome analysis of human enterovirus 71 and coxsackievirus A16 from children with hand, foot and mouth disease in Thailand during 2008-2011

  • Jiratchaya Puenpa
  • Apiradee Theamboonlers
  • Sumeth Korkong
  • Piyada Linsuwanon
  • Chittima Thongmee
  • Susheera Chatproedprai
  • Yong Poovorawan
Original Article


Hand, foot and mouth disease (HFMD) has mostly been caused by enterovirus 71 (EV71) and coxsackievirus A16 (CA16). CA 16 was the most common cause of HFMD in 2010. EV71 had a high prevalence in 2008-2009 and has been identified with a higher frequency since 2011. Nearly complete genome sequences of three EV71 strains (2008-2009 strains) and two CA16 strains (2010 strains) obtained from outbreaks in Thailand in 2008 to 2010 were characterized. Based on a phylogenetic tree of the complete VP1 region, three EV71 strains grouped into the B5, C1 and C4 genotypes, and two CA16 strains grouped into the C genotype. Based on sequence analysis, nucleotide changes were found to cluster in the internal ribosome entry site (IRES) element of the 5′-untranslated region (5′-UTR). Amino acid differences identified in all strains were located in the non-structural protein. These data also provide the molecular epidemiology of EV71 and CA16 outbreaks in Thailand.

Supplementary material

705_2011_1098_MOESM1_ESM.tif (79 kb)
Supplementary material 1 (TIFF 78 kb)
705_2011_1098_MOESM2_ESM.doc (54 kb)
Supplementary material 2 (DOC 53 kb)


  1. 1.
    Brown BA, Oberste MS, Alexander JP Jr, Kennett ML, Pallansch MA (1999) Molecular epidemiology and evolution of enterovirus 71 strains isolated from 1970 to 1998. J Virol 73:9969–9975PubMedGoogle Scholar
  2. 2.
    Brown BA, Pallansch MA (1995) Complete nucleotide sequence of enterovirus is distinct from poliovirus. Virus Res 39:195–205PubMedCrossRefGoogle Scholar
  3. 3.
    Cardosa MJ, Perera D, Brown BA, Cheon D, Chan HM, Chan KP, Cho H, McMinn P (2003) 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 9:461–468PubMedGoogle Scholar
  4. 4.
    Chang GH, Lin L, Luo YJ, Cai LJ, Wu XY, Xu HM, Zhu QY (2010) Sequence analysis of six enterovirus 71 strains with different virulences in humans. Virus Res 151:66–73PubMedCrossRefGoogle Scholar
  5. 5.
    Chang LY, Huang LM, Gau SS, Wu YY, Hsia SH, Fan TY, Lin KL, Huang YC, Lu CY, Lin TY (2007) Neurodevelopment and cognition in children after enterovirus 71 infection. N Engl J Med 356:1226–1234PubMedCrossRefGoogle Scholar
  6. 6.
    Chatproedprai S, Theanboonlers A, Korkong S, Thongmee C, Wananukul S, Poovorawan Y (2010) Clinical and molecular characterization of hand-foot-and-mouth disease in Thailand, 2008–2009. Jpn J Infect Dis 63:229–233PubMedGoogle Scholar
  7. 7.
    Chen X, Zhang Q, Li J, Cao W, Zhang JX, Zhang L, Zhang W, Shao ZJ, Yan Y (2010) Analysis of recombination and natural selection in human enterovirus 71. Virology 398:251–261PubMedCrossRefGoogle Scholar
  8. 8.
    Chumakov M, Voroshilova M, Shindarov L (1979) Enterovirus 71 isolated from cases of epidemic poliomyelitis-like disease in Bulgaria. Arch Virol 60:329–340PubMedCrossRefGoogle Scholar
  9. 9.
    Foo DG, Alonso S, Phoon MC, Ramachandran NP, Chow VT, Poh CL (2007) Identification of neutralizing linear epitopes from the VP1 capsid protein off enterovirus 71 using synthetic peptides. Virus Res 125:61–68PubMedCrossRefGoogle Scholar
  10. 10.
    Foo DG, Macary PA, Alonso S, Poh CL (2008) Identification of human CD4 T-cell epitopes on the VP1 capsid protein of enterovirus 71. Viral Immunol 21:215–224PubMedCrossRefGoogle Scholar
  11. 11.
    Grist NR, Bell EJ, Assaad F (1978) Enteroviruses in human disease. Prog Med Virol 24:114–157PubMedGoogle Scholar
  12. 12.
    Herrero LJ, Lee CSM, Hurrelbrink RJ, Chua BH, Chua KB, McMinn PC (2003) Molecular epidemiology of enterovirus 71 in peninsular Malaysia, 1997–2000. Arch Virol 148:1369–1385PubMedCrossRefGoogle Scholar
  13. 13.
    Hosoya M, Kawasaki Y, Sato M, Honzumi K, Hayashi A, Hiroshima T, Ishiko H, Kato K, Suzuki H (2007) Genetic diversity of coxsackievirus A16 associated with hand, foot, and mouth disease epidemics in Japan from 1983 to 2003. J Clin Microbiol 45:112–120PubMedCrossRefGoogle Scholar
  14. 14.
    Huang SW, Hsu YW, Smith DJ, Kiang D, Tsai HP, Lin KH, Wang SM, Liu CC, Su IJ, Wang JR (2009) Reemergence of enterovirus 71 in 2008 in Taiwan: dynamics of genetic and antigenic evolution from 1998 to 2008. J Clin Microbiol 47:3653–3662PubMedCrossRefGoogle Scholar
  15. 15.
    Huang YP, Lin TL, Kuo CY, Lin MW, Yao CY, Liao HW, Hsu LC, Yang CF, Yang JY, Chen PJ, Wu HS (2008) The circulation of subgenogroups B5 and C5 of enterovirus 71 in Taiwan from 2006 to 2007. Virus Res 137:206–212PubMedCrossRefGoogle Scholar
  16. 16.
    Li L, He Y, Yang H, Zhu J, Xu X, Dong J, Zhu Y, Jin Q (2005) Genetic characteristics of human enterovirus 71 and coxsackievirus A16 circulating from 1999 to 2004 in Shenzhen, People’s Republic of China. J Clin Microbiol 43:3835–3839PubMedCrossRefGoogle Scholar
  17. 17.
    McMinn PC (2002) An overview of the evolution of enterovirus 71 and its clinical and public health significance. FEMS Microbiol Rev 26:91–107PubMedCrossRefGoogle Scholar
  18. 18.
    Mizuta K, Abiko C, Murata T, Matsuzuki Y, Itagaki T, Sanjoh K, Sakamoto M, Hongo S, Murayama S, Hayasaka K (2005) Frequent importation of enterovirus 71 from surrounding countries into the local community of Yamagata, Japan, between 1998 and 2003. J Clin Microbiol 43:6171–6175PubMedCrossRefGoogle Scholar
  19. 19.
    Nagy G, Takatsy S, Kukan E, Mihaly I, Domok I (1982) Virological diagnosis of enterovirus type 71 infections: experiences gained during an epidemic of acute CNS diseases in Hungary in 1978. Arch Virol 71:217–227PubMedCrossRefGoogle Scholar
  20. 20.
    Perera D, Yusof MA, Podin Y, Ooi MH, Thao NT, Wong KK, Zaki A, Chua KB, Malik YA, Tu PV, Tien NT, Puthavathana P, McMinn PC, Cardosa MJ (2007) Molecular phylogeny of modern coxsackievirus A16. Arch Virol 152:1201–1208PubMedCrossRefGoogle Scholar
  21. 21.
    Ranganathan S, Singh S, Poh CL, Chow VT (2002) The hand, foot and mouth disease virus capsid: sequence analysis and prediction of antigenic sites from homology modeling. Appl Bioinform 1:43–52Google Scholar
  22. 22.
    Schmidt NJ, Lennette EH, Ho HH (1974) An apparently new enterovirus isolated from patients with disease of the central nervous system. J Infect Dis 129:304–309PubMedCrossRefGoogle Scholar
  23. 23.
    Shimizu H, Utama A, Onnimala N, Li C, Li-Bi Z, Yu-Jie M, Pongsuwanna Y, Miyamura T (2004) Molecular epidemiology of enterovirus 71 infection in the Western Pacific Region. Pediatr Int 46:231–235PubMedCrossRefGoogle Scholar
  24. 24.
    Svitkin YV, Maslova SV, Agol VI (1985) The genomes of attenuated and virulent poliovirus strains differ in their in vitro translation efficiencies. Virology 147:243–252PubMedCrossRefGoogle Scholar
  25. 25.
    Svitkin YV, Pestova T, Maslova SV, Agol VI (1988) Point mutations modify the response of poliovirus RNA to a translation initiation factor: a comparison of neurovirulent and attenuated strains. Virology 166:394–404PubMedCrossRefGoogle Scholar
  26. 26.
    Svitkin YV, Cammack N, Minor PD, Almond JW (1990) Translation deficiency of the Sabin type 3 poliovirus genome: association with an attenuating mutation C472-U. Virology 175:103–109PubMedCrossRefGoogle Scholar
  27. 27.
    Tamura K, Dudley J, Nei M, Kumar S (2007) MEGA4: molecular evolutionary genetics analysis (MEGA) software version 4.0. Mol Biol Evol 24:1596–1599PubMedCrossRefGoogle Scholar
  28. 28.
    Thai National Institute of Health (2007) Annual epidemiology and surveillance report. Bureau of epidemiology. Accessed 21 March 2011 (in Thai)
  29. 29.
    Thompson SR, Sarnow P (2003) Enterovirus 71 contains a type I IRES element that functions when eukaryotic initiation factor eIF4G is cleaved. Virology 315:259–266PubMedCrossRefGoogle Scholar
  30. 30.
    Tu PV, Thao NT, Perera D, Huu TK, Tien NT, Thuong TC, How OM, Cardosa MJ, McMinn PC (2007) Epidemiologic and virologic investigation of hand, foot and mouth disease, southern Vietnam, 2005. Emerg Infect Dis 13:1733–1741PubMedGoogle Scholar
  31. 31.
    Yang F, Ren L, Xiong Z, Li J, Xiao Y, Zhao R, He Y, Bu G, Zhou S, Wang J, Qi J (2009) Enterovirus 71 outbreak in the People’s Republic of China in 2008. J Clin Microbiol 47:2351–2352PubMedCrossRefGoogle Scholar
  32. 32.
    Zoll J, Heus HA, van Kuppeveld FJ, Melchers WJ (2009) The structure-function relationship of the enterovirus 3′-UTR. Virus Res 139:209–216PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Jiratchaya Puenpa
    • 1
  • Apiradee Theamboonlers
    • 1
  • Sumeth Korkong
    • 1
  • Piyada Linsuwanon
    • 1
  • Chittima Thongmee
    • 1
  • Susheera Chatproedprai
    • 1
  • Yong Poovorawan
    • 1
  1. 1.Department of Pediatrics, Center of Excellence in Clinical Virology, Faculty of MedicineChulalongkorn UniversityBangkokThailand

Personalised recommendations