Department of Pathology, Center for Tropical Diseases, Center for Biodefense and Emerging Diseases, Institute for Human Infections and Immunity, and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA.
J Virol. 2014 Apr;88(8):4522-32. doi: 10.1128/JVI.02686-13. Epub 2014 Feb 5.
In recent years, genotype I (GI) of Japanese encephalitis virus (JEV) has displaced genotype III (GIII) as the dominant virus genotype throughout Asia. In this study, the largest collection of GIII and GI envelope gene-derived viral sequences assembled to date was used to reconstruct the spatiotemporal chronology of genotype displacement throughout Asia and to determine the evolutionary and epidemiological dynamics underlying this significant event. GI consists of two clades, GI-a and GI-b, with the latter being associated with displacement of GIII as the dominant JEV genotype throughout Asia in the 1990s. Phylogeographic analysis indicated that GI-a diverged in Thailand or Cambodia and has remained confined to tropical Asia, whereas GI-b diverged in Vietnam and then dispersed northwards to China, where it was subsequently dispersed to Japan, Korea, and Taiwan. Molecular adaptation was detected by more than one method at one site (residue 15), and coevolution was detected at two pairs of sites (residues 89 to 360 and 129 to 141) within the GI E gene protein alignment. Viral multiplication and temperature sensitivity analyses in avian and mosquito cells revealed that the GI-b isolate JE-91 had significantly higher infectivity titers in mosquito cells from 24 to 48 h postinfection than did the GI-a and GIII isolates. If the JE-91 isolate is indeed representative of GI-b, an increased multiplicative ability of GI-b viruses compared to that of GIII viruses early in mosquito infection may have resulted in a shortened extrinsic incubation period that led to an increased number of GI enzootic transmission cycles and the subsequent displacement of GIII.
Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, represents the most significant etiology of childhood viral neurological infection in Asia. Despite the existence of effective vaccines, JEV is responsible for an estimated 68,000 human cases and a reported 10,000 to 15,000 deaths annually. Phylogenetic studies divided JEV into five geographically and epidemiologically distinct genotypes (GI to GV). GIII has been the source of numerous JEV epidemics throughout history and was the most frequently isolated genotype throughout most of Asia from 1935 until the 1990s. In recent years, GI has displaced GIII as the most frequently isolated virus genotype. To date, the mechanism of this genotype replacement has remained unknown. In this study, we have identified genetic determinants underlying the genotype displacement as it unfolded across Asia. JEV provides a paradigm for other flaviviruses, including West Nile, yellow fever, and dengue viruses, and the critical role of the selective advantages in the mosquito vector.
日本脑炎病毒（JEV）是一种蚊媒黄病毒，是亚洲儿童病毒性神经感染的主要病因。尽管存在有效的疫苗，但 JEV 每年仍估计导致 68000 例人类病例和 10000 至 15000 例死亡。系统进化研究将 JEV 分为五个具有地理和流行病学差异的基因型（GI 至 GV）。GIII 一直是历史上许多 JEV 流行的源头，并且从 1935 年到 20 世纪 90 年代，它一直是亚洲大部分地区最常分离到的基因型。近年来，GI 取代了 GIII，成为最常分离到的病毒基因型。迄今为止，这种基因型替换的机制仍不清楚。在本研究中，我们已经确定了在亚洲各地发生的基因型替换的遗传决定因素。JEV 为其他黄病毒（包括西尼罗河病毒、黄热病病毒和登革热病毒）提供了范例，提示了在蚊媒中的选择优势的关键作用。
