No abstract

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...

The two versions of the MHINT are the first standardized Mandarin sentence speech intelligibility tests. Similar to other language versions of the HINT, the MHINT was developed using the same rationale as the English HINT, allowing norm-referenced results for the MHINT to be compared directly with results in other languages. The MHINT would benefit from further evaluation of its validity.