**2. Epidemiological features**

JE is believed to be originated in Indonesia and Malaysia long back in mid 1500s [Weaver *et al*., 1999; Sinniah *et al*., 1989]. JEV leads to major outbreaks in both temperate regions of Asia like China, Japan, Korea, Philippines, Taiwan and tropical regions like Bangladesh, India, Sri Lanka and Nepal [Bista *et al*., 2005]. The cases of JE are also reported in newer geographical regions in the Torres Strait islands of Australia and in Papua New Guinea [Fig. 1]. The reason for this wide spread of JE is unknown but it may be due to population shift or variations in agricultural practices, animal husbandry, climate, ecology or migratory birds patterns. In India the first case of JE was seen in 1955. JE is reported to be endemic in many parts such as Assam, Bihar, Madhya Pradesh, Tamil Nadu, Uttar Pradesh and West Bengal.

**3. Viral replication and morphogenesis**

**Figure 2.** Organization of the JEV genome

JEV virion comprises of a single strand of positive-sense RNA of around 11kb, enclosed in a nucleocapsid and surrounded by envelope made up of glycoproteins [Agrawal *et al*., 2013; Ye *et al*., 2012]. The RNA consists of a short 5' untranslated region (UTR), a longer 3' UTR and a single open reading frame between them. It encodes 3432 aminoacid polyprotein, which is translationally and post translationally cleaved by viral and host proteases into three structural proteins (core-C, pre-membrane-PrM and envelope-E) and seven nonstructural (NS) proteins

Japanese Encephalitis: A Neglected Viral Disease and Its Impact on Global Health

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The C protein of 12-14 kDa in size is highly basic and fuses with the RNA to form the nucleo‐ capsid. The PrM is in close proximity with the E protein, forming a heterodimer and is believed to act as a 'chaperone' to it, hindering its function until after virion release. Just before the virion release, the PrM protein is cleaved by a protease to its mature M protein form. This alteration contributes for the formation and activation of E protein homodimers. Researchers suggested that the extremely conserved N glycosylation motif N15-X16-T17 in JEV PrM and its N-glycan substituents are essential for several stages of JEV biology: PrM biogenesis, virus release and pathogenesis. The E protein is the largest structural protein, comprising of approximately 500 aminoacids, with up to two potential glycosylation sites. It is the main target

(NS1,NS2A,NS2B,NS3,NS4A,NS4B and NS5) [Fig 2][Yang *et al*., 2013].

**Figure 1.** Epidemiology of JE globally. The areas highlighted in red display the endemic regions affected by JE.
