Japanese encephalitis virus (JEV), a mosquito-borne zoonotic pathogen, is one of the major causes of viral encephalitis worldwide. Previous phylogenetic studies based on the envelope protein indicated that there are four genotypes, and surveillance data suggest that genotype I is gradually replacing genotype III as the dominant strain. Here we report an evolutionary analysis based on 98 full-length genome sequences of JEV, including 67 new samples isolated from humans, pigs, mosquitoes, midges. and bats in affected areas. To investigate the relationships between the genotypes and the significance of genotype I in recent epidemics, we estimated evolutionary rates, ages of common ancestors, and population demographics. Our results indicate that the genotypes diverged in the order IV, III, II, and I and that the genetic diversity of genotype III has decreased rapidly while that of genotype I has increased gradually, consistent with its emergence as the dominant genotype.Japanese encephalitis virus (JEV), a member of the genus Flavivirus in the family Flaviviridae, is a major cause of viral encephalitis and is endemic in several regions of Asia and the Pacific (4, 13), causing an estimated 35,000 to 50,000 infections and 10,000 to 15,000 deaths annually (4, 13, 27). Fifty percent of survivors suffer from lingering neurological effects (7,27,30). Japanese encephalitis (JE) was first reported in Japan in 1924, and JE cases were subsequently reported in many other Asian countries (4,6,7,13,22,27,30). JE was first reported in Australia in 1995 (8, 9, 31). Thus, JE has become a major cause of mosquito-transmitted viral encephalitis on two continents (15,16,25).JEV, the pathogen of JE, has a genome comprising a positive-sense, single-stranded RNA molecule of approximately 11 kb that is capped at the 5Ј end and is not polyadenylated at the 3Ј end. It carries a single open reading frame (ORF) encoding a polyprotein that is processed into three structural (C, M, and E) and seven nonstructural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) proteins, flanked by 5Ј and 3Ј nontranslated regions (NTRs) (13).Until the latter part of the 20th century, studies indicated that the predominant genotype was genotype III. Since then, there have been multiple reports of genotype I displacing genotype III in many regions (12,18,19,20,24,32,34,35), and in many areas genotype I is now recognized as the dominant strain.As part of a national encephalitis surveillance program, we collected samples from a variety of vectors (mosquitoes and midges), host animals (bats and pigs), and patients with cases of encephalitis in areas where the disease is epidemic, and we isolated viruses from a selection of the JEV-positive samples and sequenced their full genomes. We combined these sequences with other, publicly available full-length genome sequences for a final set of 98 genome sequences. With this set we performed the first detailed evolutionary analysis of JEV based on full-length genome sequences and investigated the epidemiology of genotype I relati...

Slave trading of Africans to the Americas, during the 16th to the 19th century was responsible for the first recorded emergence in the New World of two arthropod-borne viruses (arboviruses), yellow fever virus and dengue virus. Many other arboviruses have since emerged from their sylvatic reservoirs and dispersed globally due to evolving factors that include anthropological behaviour, commercial transportation and land-remediation. Here, we outline some characteristics of these highly divergent arboviruses, including the variety of life cycles they have developed and the mechanisms by which they have adapted to evolving changes in habitat and host availability. We cite recent examples of virus emergence that exemplify how arboviruses have exploited the consequences of the modern human lifestyle. Using our current understanding of these viruses, we also attempt to demonstrate some of the limitations encountered in developing control strategies to reduce the impact of future emerging arbovirus diseases. Finally, we present recommendations for development by an international panel of experts reporting directly to World Health Organization, with the intention of providing internationally acceptable guidelines for improving emerging arbovirus disease control strategies. Success in these aims should alleviate the suffering and costs encountered during recent decades when arboviruses have emerged from their sylvatic environment.

The major arboviral diseases in mainland China include Japanese encephalitis, dengue fever, Crimean-Congo hemorrhagic fever (also known as Xinjiang hemorrhagic fever), and tick-borne encephalitis. These and other newly found arbovirus infections due to Banna virus and Tahyna virus contribute to a large and relatively neglected disease burden in China. Here we briefly review the literature regarding these arboviral infections in mainland China with emphasis on their epidemiology, primary vectors, phylogenetic associations, and the prevention programs associated with these agents in China.

BackgroundThe current Japanese encephalitis (JE) vaccine derived from G3 JE virus (JEV) can induce protective immunity against G1–G4 JEV genotypes. However, protective efficacy against the emerging G5 genotype has not been reported.Methods/Principal FindingsUsing in vitro and in vivo tests, biological phenotype and cross-immunoreactions were compared between G3 JEV and G5 JEV (wild strains). The PRNT90 method was used to detect neutralizing antibodies against different genotypes of JEV in JE vaccine-immunized subjects and JE patients. In JE vaccine-immunized mice, the lethal challenge protection rates against G3 and G5 JEV wild strains were 100% and 50%, respectively. The seroconversion rates (SCRs) of virus antibodies against G3 and G5 JEV among vaccinated healthy subjects were 100% and 35%, respectively. All clinically identified JE patients showed high levels of G3 JEV neutralizing antibodies (≥1:10–1280) with positive serum geometric mean titers (GMTs) of 43.2, while for G5 JEV, neutralizing antibody conversion rates were only 64% with positive serum GMTs of 11.14. Moreover, the positive rate of JEV neutralizing antibodies against G5 JEV in pediatric patients was lower than in adults.Conclusions/SignificanceLow levels of neutralizing/protective antibodies induced by the current JE vaccine, based on the G3 genotype, were observed against the emerging G5 JEV genotype. Our results demonstrate the need for more detailed studies to reevaluate whether or not the apparent emergence of G5 JEV can be attributed to failure of the current vaccine to induce appropriate immune protectivity against this genotype of JEV.

Japanese encephalitis virus (JEV) is a representative virus of the JEV serogroup in genus Flavivirus, family Flaviviridae. JEV is a mosquito-borne virus that causes Japanese encephalitis (JE), one of the most severe viral encephalitis diseases in the world. JEV is divided into five genotypes (G1-G5), and each genotype has its own distribution pattern. However, the distribution of different JEV genotypes has changed markedly in recent years. JEV G1 has replaced G3 as the dominant genotype in the traditional epidemic areas in Asia, while G3 has spread from Asia to Europe and Africa and caused domestic JE cases in Africa. G2 and G5, which were endemic in Malaysia, exhibited great geographical changes as well. G2 migrated southward and led to prevalence of JE in Australia, while G5 emerged in China and South Korea after decades of silence. Along with these changes, JE occurred in some non-traditional epidemic regions as an emerging infectious disease. The regional changes in JEV pose a great threat to human health, leading to huge disease burdens. Therefore, it is of great importance to strengthen the monitoring of JEV as well as virus genotypes, especially in non-traditional epidemic areas.

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BackgroundAlthough a previous study predicted that Japanese encephalitis virus (JEV) originated in the Malaysia/Indonesia region, the virus is known to circulate mainly on the Asian continent. However, there are no reported systematic studies that adequately define how JEV then dispersed throughout Asia.Methodology/Principal FindingsIn order to understand the mode of JEV dispersal throughout the entire Asian continent and the factors that determine the dispersal characteristics of JEV, a phylogenetic analysis using Bayesian Markov chain Monte Carlo simulations was conducted on all available JEV E gene sequences in GenBank, plus strains recently isolated in China. Here we demonstrate for the first time that JEV lineages can be divided into four endemic cycles, comprising southern Asia, eastern coastal Asia, western Asia, and central Asia. The isolation places of the viruses in each endemic cycle were geographically independent regardless of years, vectors, and hosts of isolation. Following further analysis, we propose that the southernmost region (Thailand, Vietnam, and Yunnan Province, China) was the source of JEV transmission to the Asian continent following its emergence. Three independent transmission routes from the south to north appear to define subsequent dispersal of JEV. Analysis of JEV population dynamics further supports these concepts.Conclusions/SignificanceThese results and their interpretation provide new insights into our understanding of JEV evolution and dispersal and highlight its potential for introduction into non-endemic areas.

Japanese encephalitis (JE) is arguably one of the most serious viral encephalitis diseases worldwide. China has a long history of high prevalence of Japanese encephalitis, with thousands of cases reported annually and incidence rates often exceeding 15/100,000. In global terms, the scale of outbreaks and high incidence of these pandemics has almost been unique, placing a heavy burden on the Chinese health authorities. However, the introduction of vaccines, developed in China, combined with an intensive vaccination program initiated during the 1970s, as well as other public health interventions, has dramatically decreased the incidence from 20.92/100,000 in 1971, to 0.12/100,000 in 2011. Moreover, in less readily accessible areas of China, changes to agricultural practices designed to reduce chances of mosquito bites as well as mosquito population densities have also been proven effective in reducing local JE incidence. This unprecedented public health achievement has saved many lives and provided valuable experience that could be directly applicable to the control of vector-borne diseases around the world. Here, we review and discuss strategies for promotion and expansion of vaccination programs to reduce the incidence of JE even further, for the benefit of health authorities throughout Asia and, potentially, worldwide.