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. 2015 Aug 18;30(4):277–289. doi: 10.1007/s12250-015-3621-4

Investigation of the genotype III to genotype I shift in Japanese encephalitis virus and the impact on human cases

Na Han 3,4, James Adams 2, Wei Fang 1, Si-Qing Liu 1, Simon Rayner 1,2,✉
PMCID: PMC8200877  PMID: 26311492

Abstract

Japanese encephalitis is a mosquito borne disease and is the leading cause of viral encephalitis in the Asia-Pacific area. The causative agent, Japanese encephalitis virus (JEV) can be phylogenetically classified into five genotypes based on nucleotide sequence. In recent years, genotype I (GI) has displaced genotype III (GIII) as the dominant lineage, but the mechanisms behind this displacement event requires elucidation. In an earlier study, we compared host variation over time between the two genotypes and observed that GI appears to have evolved to achieve more efficient infection in hosts in the replication cycle, with the tradeoff of reduced infectivity in secondary hosts such as humans. To further investigate this phenomenon, we collected JEV surveillance data on human cases and, together with sequence data, and generated genotype/case profiles from seven Asia-Pacific countries and regions to characterize the GI/GIII displacement event. We found that, when comprehensive and consistent vaccination and surveillance data was available, and the GIII to GI shift occurred within a well-defined time period, there was a statistically significant drop in JEV human cases. Our findings provide further support for the argument that GI is less effective in infecting humans, who represent a dead end host. However, experimental investigation is necessary to confirm this hypothesis. The study highlights the value of alternative approaches to investigation of epidemics, as well as the importance of effective data collection for disease surveillance and control.

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s12250-015-3621-4 and is accessible for authorized users.

Keywords: flavivirus, Japanese encephalitis virus (JEV), bioinformatics, epidemiology, lineage replacement

Electronic supplementary material

12250_2015_3621_MOESM1_ESM.pdf (546.1KB, pdf)

Supplementary material, approximately 617 KB.

Footnotes

ORCID: 0000-0001-8703-9140

References

  1. Angami K, Chakravarty SK, Das MS, Chakraborty MS, Mukherjee KK. Seroepidemiological study of Japanese encephalitis in Dimapur, Nagaland. J Commun Dis. 1989;21:87–95. [PubMed] [Google Scholar]
  2. Arai S, Matsunaga Y, Takasaki T, Tanaka-Taya K, Taniguchi K, Okabe N, Kurane I. Japanese encephalitis: surveillance and elimination effort in Japan from 1982 to 2004. Jpn J Infect Dis. 2008;61:333–338. [PubMed] [Google Scholar]
  3. Burke DS, Leake CJ. Japanese encephalitis. In: Monath TP, editor. The Arboviruses: epidemiology and ecology. Boca Raton: CRC Press; 1988. pp. 63–92. [Google Scholar]
  4. Campbell GL, Hills SL, Fischer M, Jacobson JA, Hoke CH, Hombach JM, Marfin AA, Solomon T, Tsai TF, Tsu VD, Ginsburg AS. Estimated global incidence of Japanese encephalitis: a systematic review. Bull World Health Organ. 2011;89:766–774. doi: 10.2471/BLT.10.085233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chakraborty AK, Chakravarti SK, Chakravarty MS. Outbreak of Japanese encephalitis in two districts of Assam during 1980: some epidemiological features. Indian J Public Health. 1987;31:5–11. [PubMed] [Google Scholar]
  6. Chattopadhyay UK. A study on the status of Japanese encephalitis infection in Arunachal Pradesh. J Commun Dis. 2001;33:261–265. [PubMed] [Google Scholar]
  7. Chen YY, Fan YC, Tu WC, Chang RY, Shih CC, Lu IH, Chien MS, Lee WC, Chen TH, Chang GJ, Chiou SS. Japanese encephalitis virus genotype replacement, Taiwan, 2009–2010. Emerg Infect Dis. 2011;17:2354–2356. doi: 10.3201/eid1712.110914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dhillon GP, Raina VK. Epidemiology of Japanese encephalitis in context with Indian scenario. J Indian Med Assoc. 2008;106:660–663. [PubMed] [Google Scholar]
  9. Dong D, Fu SH, Wang LH, Lv Z, Li TY, Liang GD. Simultaneous detection of three arboviruses using a triplex RT-PCR: enzyme hybridization assay. Virol Sin. 2012;27:179–186. doi: 10.1007/s12250-012-3246-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fulmali PV, Sapkal GN, Athawale S, Gore MM, Mishra AC, Bondre VP. Introduction of Japanese encephalitis virus genotype I, India. Emerg Infect Dis. 2011;17:319–321. doi: 10.3201/eid1702.100815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. George S, Yergolkar PN, Kamala H, Kamala CS. Outbreak of encephalitis in Bellary District of Karnataka & adjoining areas of Andhra Pradesh. Indian J Med Res. 1990;91:328–330. [PubMed] [Google Scholar]
  12. Han N, Adams J, Chen P, Guo ZY, Zhong XF, Fang W, Li N, Wen L, Tao XY, Yuan ZM, Rayner S. Comparison of genotypes I and III in Japanese encephalitis virus reveals distinct differences in their genetic and host diversity. J Virol. 2014;88:11469–11479. doi: 10.1128/JVI.02050-14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Henrich TJ, Hutchaleelaha S, Jiwariyavej V, Barbazan P, Nitatpattana N, Yoksan S, Gonzalez JP. Geographic dynamics of viral encephalitis in Thailand. Microbes Infect. 2003;5:603–611. doi: 10.1016/S1286-4579(03)00100-X. [DOI] [PubMed] [Google Scholar]
  14. Ho Dang Trung N, Le Thi Phuong T, Wolbers M, Nguyen Van Minh H, Nguyen Thanh V, Van MP, Thieu NT, Van TL, Song DT, Thi PL, Thi Phuong TN, Van CB, Tang V, Ngoc Anh TH, Nguyen D, Trung TP, Thi Nam LN, Kiem HT, Thi Thanh TN, Campbell J, Caws M, Day J, de Jong MD, Van Vinh CN, Van Doorn HR, Tinh HT, Farrar J, Schultsz C. 2012. Aetiologies of central nervous system infection in Viet Nam: a prospective provincial hospital-based descriptive surveillance study. PLoS One, 7: e37825. [DOI] [PMC free article] [PubMed]
  15. Huang JH, Lin TH, Teng HJ, Su CL, Tsai KH, Lu LC, Lin C, Yang CF, Chang SF, Liao TL, Yu SK, Cheng CH, Chang MC, Hu HC, Shu PY. Molecular epidemiology of Japanese encephalitis virus, Taiwan. Emerg Infect Dis. 2010;16:876–878. doi: 10.3201/eid1605.091055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jan LR, Yueh YY, Wu YC, Horng CB, Wang GR. Genetic variation of Japanese encephalitis virus in Taiwan. Am J Trop Med Hyg. 2000;62:446–452. doi: 10.4269/ajtmh.2000.62.446. [DOI] [PubMed] [Google Scholar]
  17. Johansson MA, Cummings DA, Glass GE. Multiyear climate variability and dengue—El Nino southern oscillation, weather, and dengue incidence in Puerto Rico, Mexico, and Thailand: a longitudinal data analysis. PLoS Med. 2009;6:e1000168. doi: 10.1371/journal.pmed.1000168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kabilan L, Vrati S, Ramesh S, Srinivasan S, Appaiahgari MB, Arunachalam N, Thenmozhi V, Kumaravel SM, Samuel PP, Rajendran R. Japanese encephalitis virus (JEV) is an important cause of encephalitis among children in Cuddalore district, Tamil Nadu, India. J Clin Virol. 2004;31:153–159. doi: 10.1016/j.jcv.2004.03.011. [DOI] [PubMed] [Google Scholar]
  19. Kar NJ, Bora D, Sharma RC, Bhattacharjee J, Datta KK, Sharma RS. Epidemiological profile of Japanese encephalitis in Gorakhpur district, Uttar Pradesh, 1982–1988. J Commun Dis. 1992;24:145–149. [PubMed] [Google Scholar]
  20. Kaur R, Agarwal CS, Das D. An investigation into the JE epidemic of 2000 in Upper Assam—a perspective study. J Commun Dis. 2002;34:135–145. [PubMed] [Google Scholar]
  21. KCDCP. (Korean Centre for Disease Control & Prevention) Public Health Weekly Report. 2012;5:491. [Google Scholar]
  22. Konishi E, Kitai Y, Nishimura K, Harada S. Follow-up survey of Japanese encephalitis virus infection in Kumamoto Prefecture, South-West Japan: status during 2009-2011. Jpn J Infect Dis. 2012;65:448–450. doi: 10.7883/yoken.65.448. [DOI] [PubMed] [Google Scholar]
  23. Kuwayama M, Ito M, Takao S, Shimazu Y, Fukuda S, Miyazaki K, Kurane I, Takasaki T. Japanese encephalitis virus in meningitis patients, Japan. Emerg Infect Dis. 2005;11:471–473. doi: 10.3201/eid1103.040285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Le Flohic G, Porphyre V, Barbazan P, Gonzalez JP. Review of climate, landscape, and viral genetics as drivers of the Japanese encephalitis virus ecology. PLoS Negl Trop Dis. 2013;7:e2208. doi: 10.1371/journal.pntd.0002208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Le VT, Phan TQ, Do QH, Nguyen BH, Lam QB, Bach V, Truong H, Tran TH, Nguyen V, Tran T, Vo M, Tran VT, Schultsz C, Farrar J, van Doorn HR, de Jong MD. Viral etiology of encephalitis in children in southern Vietnam: results of a one-year prospective descriptive study. PLoS Negl Trop Dis. 2010;4:e854. doi: 10.1371/journal.pntd.0000854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6:e1000100. doi: 10.1371/journal.pmed.1000100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Liu W, Clemens JD, Yang JY, Xu ZY. Immunization against Japanese encephalitis in China: a policy analysis. Vaccine. 2006;24:5178–5182. doi: 10.1016/j.vaccine.2006.04.006. [DOI] [PubMed] [Google Scholar]
  28. Ma SP, Yoshida Y, Makino Y, Tadano M, Ono T, Ogawa M. Short report: a major genotype of Japanese encephalitis virus currently circulating in Japan. Am J Trop Med Hyg. 2003;69:151–154. [PubMed] [Google Scholar]
  29. MHLWJ. Current status of Japanese encephalitis vaccination. 2011. [Google Scholar]
  30. Mudur G. Japanese encephalitis outbreak kills 1300 children in India. BMJ. 2005;331:1288. doi: 10.1136/bmj.331.7528.1288-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Mukherjee KK, Chakravarti SK, Mukherjee MK, De PN, Chatterjee S, Chatterjee P, Chakraborty MS. Recurrent outbreaks of Japanese encephalitis in Nagaland (1985-1989)—a seroepidemiological study. J Commun Dis. 1991;23:11–17. [PubMed] [Google Scholar]
  32. Nga PT, del Carmen Parquet M, Cuong VD, Ma SP, Hasebe F, Inoue S, Makino Y, Takagi M, Nam VS, Morita K. Shift in Japanese encephalitis virus (JEV) genotype circulating in northern Vietnam: implications for frequent introductions of JEV from Southeast Asia to East Asia. J Gen Virol. 2004;85:1625–1631. doi: 10.1099/vir.0.79797-0. [DOI] [PubMed] [Google Scholar]
  33. Nishijima N, Marusawa H, Ueda Y, Takahashi K, Nasu A, Osaki Y, Kou T, Yazumi S, Fujiwara T, Tsuchiya S, Shimizu K, Uemoto S, Chiba T. Dynamics of hepatitis B virus quasispecies in association with nucleos(t)ide analogue treatment determined by ultra-deep sequencing. PLoS One. 2012;7:e35052. doi: 10.1371/journal.pone.0035052. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Nitatpattana N, Dubot-Peres A, Gouilh MA, Souris M, Barbazan P, Yoksan S, de Lamballerie X, Gonzalez JP. Change in Japanese Encephalitis Virus Distribution, Thailand. Emerg Infect Dis. 2008;14:1762–1765. doi: 10.3201/eid1411.080542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. NVBDCP. Japanese Encephalitis cases 2008-2010. 2012. [Google Scholar]
  36. Obara M, Yamauchi T, Watanabe M, Hasegawa S, Ueda Y, Matsuno K, Iwai M, Horimoto E, Kurata T, Takizawa T, Kariwa H, Takashima I. Continuity and change of Japanese encephalitis virus in Toyama Prefecture, Japan. Am J Trop Med Hyg. 2011;84:695–708. doi: 10.4269/ajtmh.2011.10-0188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Olsen SJ, Supawat K, Campbell AP, Anantapreecha S, Liamsuwan S, Tunlayadechanont S, Visudtibhan A, Lupthikulthum S, Dhiravibulya K, Viriyavejakul A, Vasiknanonte P, Rajborirug K, Watanaveeradej V, Nabangchang C, Laven J, Kosoy O, Panella A, Ellis C, Henchaichon S, Khetsuriani N, Powers AM, Dowell SF, Fischer M. Japanese encephalitis virus remains an important cause of encephalitis in Thailand. Int J Infect Dis. 2010;14:888–892. doi: 10.1016/j.ijid.2010.03.022. [DOI] [PubMed] [Google Scholar]
  38. Pan XL, Liu H, Wang HY, Fu SH, Liu HZ, Zhang HL, Li MH, Gao XY, Wang JL, Sun XH. Emergence of Genotype I of Japanese Encephalitis Virus as the Dominant Genotype in Asia. J Virol. 2011;85:9847–9853. doi: 10.1128/JVI.00825-11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Parida M, Dash PK, Tripathi NK, Ambuj Japanese Encephalitis Outbreak, India, 2005. Emerg Infect Dis. 2006;12:1427–1430. doi: 10.3201/eid1209.060200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Phukan AC, Borah PK, Mahanta J. Japanese encephalitis in Assam, northeast India. Southeast Asian J Trop Med Public Health. 2004;35:618–622. [PubMed] [Google Scholar]
  41. Potula R, Badrinath S, Srinivasan S. Japanese encephalitis in and around Pondicherry, South India: a clinical appraisal and prognostic indicators for the outcome. J Trop Pediatr. 2003;49:48–53. doi: 10.1093/tropej/49.1.48. [DOI] [PubMed] [Google Scholar]
  42. Prasad SR, Kumar V, Marwaha RK, Batra KL, Rath RK, Pal SR. An epidemic of encephalitis in Haryana: serological evidence of Japanese encephalitis in a few patients. Indian Pediatr. 1993;30:905–910. [PubMed] [Google Scholar]
  43. Rao JS, Misra SP, Patanayak SK, Rao T D, Gupta RK, Thapar BR. Japanese Encephalitis epidemic in Anantapur district, Andhra Pradesh (October-November, 1999) J Commun Dis. 2000;32:306–312. [PubMed] [Google Scholar]
  44. Saito M, Taira K, Itokazu K, Mori N. Recent change of the antigenicity and genotype of Japanese encephalitis viruses distributed on Okinawa Island, Japan. Am J Trop Med Hyg. 2007;77:737–746. [PubMed] [Google Scholar]
  45. Sarkar A, Taraphdar D, Mukhopadhyay SK, Chakrabarti S, Chatterjee S. Serological and molecular diagnosis of Japanese encephalitis reveals an increasing public health problem in the state of West Bengal, India. Trans R Soc Trop Med Hyg. 2012;106:15–19. doi: 10.1016/j.trstmh.2011.08.011. [DOI] [PubMed] [Google Scholar]
  46. Sarkari NB, Thacker AK, Barthwal SP, Mishra VK, Prapann S, Srivastava D, Sarkari M. Japanese encephalitis (JE). Part I: clinical profile of 1,282 adult acute cases of four epidemics. J Neurol. 2012;259:47–57. doi: 10.1007/s00415-011-6118-6. [DOI] [PubMed] [Google Scholar]
  47. Saxena SK, Mishra N, Saxena R, Singh M, Mathur A. Trend of Japanese encephalitis in North India: evidence from thirty-eight acute encephalitis cases and appraisal of niceties. J Infect Dev Ctries. 2009;3:517–530. doi: 10.3855/jidc.470. [DOI] [PubMed] [Google Scholar]
  48. Schuh AJ, Ward MJ, Leigh Brown AJ, Barrett AD. J Virol. 2014. Dynamics of the emergence and establishment of a newly dominant genotype of Japanese encephalitis virus throughout Asia. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Seo HJ, Kim HC, Klein TA, Ramey AM, Lee JH, Kyung SG, Park JY, Cho YS, Cho IS, Yeh JY. Molecular Detection and Genotyping of Japanese Encephalitis Virus in Mosquitoes during a 2010 Outbreak in the Republic of Korea. PLoS One. 2013;8:e55165. doi: 10.1371/journal.pone.0055165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Shrivastva A, Tripathi NK, Parida M, Dash PK, Jana A L, Rao PV. Comparison of a dipstick enzyme-linked immunosorbent assay with commercial assays for detection of Japanese encephalitis virus-specific IgM antibodies. J Postgrad Med. 2008;54:181–185. doi: 10.4103/0022-3859.40959. [DOI] [PubMed] [Google Scholar]
  51. Sohn YM. Japanese encephalitis immunization in South Korea: past, present, and future. Emerg Infect Dis. 2000;6:17–24. doi: 10.3201/eid0601.000103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Solomon T, Thao TT, Lewthwaite P, Ooi MH, Kneen R, Dung NM, White N. A cohort study to assess the new WHO Japanese encephalitis surveillance standards. Bull World Health Organ. 2008;86:178–186. doi: 10.2471/BLT.07.043307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Takhampunya R, Kim HC, Tippayachai B, Kengluecha A, Klein TA, Lee WJ, Grieco J, Evans BP. Emergence of Japanese encephalitis virus genotype V in the Republic of Korea. Virol J. 2011;8:449. doi: 10.1186/1743-422X-8-449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Tang WF, Ogawa M, Eshita Y, Aono H, Makino Y. Molecular evolution of Japanese encephalitis virus isolates from swine in Oita, Japan during 1980-2009. Infect Genet Evol. 2010;10:329–336. doi: 10.1016/j.meegid.2009.12.005. [DOI] [PubMed] [Google Scholar]
  55. Thakare JP, Shenoy SR, Padbidri VS, Rajput CS, Karmarkar DP, Deo SS. Japanese encephalitis in Sangli district, Maharashtra. Indian J Med Res. 1999;109:165–166. [PubMed] [Google Scholar]
  56. Tiwari S, Singh RK, Tiwari R, Dhole TN. Japanese encephalitis: a review of the Indian perspective. Braz J Infect Dis. 2012;16:564–573. doi: 10.1016/j.bjid.2012.10.004. [DOI] [PubMed] [Google Scholar]
  57. TMPH. Thailand Health Profile Report 2008-2010. 2012. p. 171. [Google Scholar]
  58. Tsai TF. New initiatives for the control of Japanese encephalitis by vaccination: minutes of a WHO/CVI meeting, Bangkok, Thailand, 13-15 October 1998. Vaccine. 2000;18(2):1–25. doi: 10.1016/S0264-410X(00)00037-2. [DOI] [PubMed] [Google Scholar]
  59. Umenai T, Krzysko R, Bektimirov TA, Assaad FA. Japanese encephalitis: current worldwide status. Bull World Health Organ. 1985;63:625–631. [PMC free article] [PubMed] [Google Scholar]
  60. Vajpayee A, Dey PN, Chakraborty AK, Chakraborty MS. Study of the outbreak of Japanese encephalitis in Lakhimpur district of Assam in 1989. J Indian Med Assoc. 1992;90:114–115. [PubMed] [Google Scholar]
  61. Vajpayee A, Mukherjee MK, Chakraborty AK, Chakraborty MS. Investigation of an outbreak of Japanese encephalitis in Rourkela City (Orissa) during 1989. J Commun Dis. 1991;23:18–21. [PubMed] [Google Scholar]
  62. Yen NT, Duffy MR, Hong NM, Hien NT, Fischer M, Hills SL. Surveillance for Japanese encephalitis in Vietnam, 1998-2007. Am J Trop Med Hyg. 2010;83:816–819. doi: 10.4269/ajtmh.2010.10-0262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Yun SM, Cho JE, Ju YR, Kim SY, Ryou J, Han MG, Choi WY, Jeong YE. Molecular epidemiology of Japanese encephalitis virus circulating in South Korea, 1983-2005. Virol J. 2010;7:127. doi: 10.1186/1743-422X-7-127. [DOI] [PMC free article] [PubMed] [Google Scholar]

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