Genetic Evolution of Japanese Encephalitis Virus

Abstract

Japanese encephalitis (JE) is widely distributed in most areas of Asia, particularly in eastern, southern, and southeastern Asia (Rosen 1986). It expanded to the Torres Strait of northern Australia in 1999, and has now become widespread in Australia (Mackenzie, 1999; Mackenzie et al., 2004). Mass vaccinations were implemented in a number of Asian countries such as Japan, Korea, China, Taiwan, Thailand, and India, leading to declines in the incidences of JE (Wu et al., 1999; Monath, 2002; Erlanger et al., 2009). Generally, swine serve as an amplifying host in the transmission cycle of the JE virus (JEV) (fig. 1), giving it an important role in the maintenance of the JEV in nature (Nidaira et al., 2009). Due to changes in the socioeconomic status, households that breed swine have sharply decreased in Japan and many other countries (Yoshida et al., 2005). Despite, an estimated 3 billion persons living in countries with endemic JE, it causes about 30,000~50,000 cases per year (Solomom, 2004; van den Hurk et al., 2008); among these, there are estimated to be 10,000~15,000 human deaths yearly worldwide (Erlanger et al., 2009). The potential for the emergence of frontiers of JEV is now a new concern (Nett et al., 2009; van den Hurk et al., 2009). The etiological agent of JE is one of about 70 members of the genus Flavivirus that belongs to the family Flaviviridae (Monath & Heinz, 1996). JEV frequently causes encephalitic diseases through bites by rice-field breeding Culex mosquitoes (van den Hurk et al., 2009; Unni et al., 2011), especially Culex tritaeneorhynchus which is a species that breeds in paddy fields (Lindenbach & Rice, 2001). This suggests that most species of JE vectors are rural mosquitoes. In association with seasonal fluctuations in mosquito population densities, JE cases mostly appear during the summer, particularly May to October in most endemic areas (Rosen, 1986). In spite of this, other mosquitoes classified in different genera including Armigeres, Aedes, Anopheles, and Mansonia have also been documented to be a potential vector (Chen et al., 2000; Deng et al., 2009; Weng et al., 1999). The JE virion is about ca. 50 nm in diameter (Westaway et al., 1985); its genome contains linear, single-stranded positive-sense RNA (~11 kb in length) (Chambers et al., 1990). The genomic RNA of the JEV comprises a 5′ untranslated region (UTR), a longer 3′ UTR, and an intervening single open reading frame (ORF) (Chambers et al., 1990) that encodes 3 structural proteins in the order of the capsid (C), membrane (prM/M), and envelope (E), followed by 7 non-structural proteins (NS1~NS5) (Chambers et al., 1990; Sumiyoshi et al., 1987). The functions of some viral proteins are now clearer. Among these, protein E is the