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Journal of Virology, March 2003, p. 3091-3098, Vol. 77, No. 5
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.5.3091-3098.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Origin and Evolution of Japanese Encephalitis Virus in Southeast Asia

Tom Solomon,1,2,3* Haolin Ni,3 David W. C. Beasley,3 Miquel Ekkelenkamp,3 Mary Jane Cardosa,4 and Alan D. T. Barrett3

Department of Neurological Science, University of Liverpool, Liverpool L9 7LJ,1 Department of Medical Microbiology, University of Liverpool, Liverpool L69 3GA, United Kingdom,2 World Health Organization Collaborating Center for Tropical Diseases, Sealy Center for Vaccine Development, and Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-0609,3 Universiti Malaysia Sarawak, 94300 Kota Samarahan, Sarawak, Malaysia4

Received 19 August 2002/ Accepted 2 December 2002

Since it emerged in Japan in the 1870s, Japanese encephalitis has spread across Asia and has become the most important cause of epidemic encephalitis worldwide. Four genotypes of Japanese encephalitis virus (JEV) are presently recognized (representatives of genotypes I to III have been fully sequenced), but its origin is not known. We have determined the complete nucleotide and amino acid sequence of a genotype IV Indonesian isolate (JKT6468) which represents the oldest lineage, compared it with other fully sequenced genomes, and examined the geographical distribution of all known isolates. JKT6468 was the least similar, with nucleotide divergence ranging from 17.4 to 19.6% and amino acid divergence ranging from 4.7 to 6.5%. It included an unusual series of amino acids at the carboxy terminus of the core protein unlike that seen in other JEV strains. Three signature amino acids in the envelope protein (including E327 Leu->Thr/Ser on the exposed lateral surface of the putative receptor binding domain) distinguished genotype IV strains from more recent genotypes. Analysis of all 290 JEV isolates for which sequence data are available showed that the Indonesia-Malaysia region has all genotypes of JEV circulating, whereas only more recent genotypes circulate in other areas (P < 0.0001). These results suggest that JEV originated from its ancestral virus in the Indonesia-Malaysia region and evolved there into the different genotypes which then spread across Asia. Our data, together with recent evidence on the origins of other emerging viruses, including dengue virus and Nipah virus, imply that tropical southeast Asia may be an important zone for emerging pathogens.

* Corresponding author. Mailing address: Department of Neurological Science, University of Liverpool, Walton Centre for Neurology and Neurosurgery, Liverpool L9 7LJ, United Kingdom. Phone: 44 (0) 151 529 5460. Fax: 44 (0) 151 529 5465. E-mail: tsolomon{at}liv.ac.uk.

Journal of Virology, March 2003, p. 3091-3098, Vol. 77, No. 5
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.5.3091-3098.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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