Background:Japanese encephalitis (JE) is one of the most important zoonotic diseases in a cosmopolitan manner.  Japanese encephalitis virus (JEV) infection represents at least 70 % of emerging diseases caused by the mosquito-borne  JEV. Nearly 20-30% of case fatality corroborated in JEV infections with 30-50% neurologic and psychiatric disorders. A strong epidemic distribution is observed mainly in South-East Asia, demonstrating typical seasonal characteristics and occasional outbreaks. Depending on the genetic diversity, geographical distribution, and emerging natures of JEV, the disease surveillance, and immunization strategies are also varied. Uncontrolled population growth, haphazard agro-animal farming, and ecological imbalance steer the emergence and reemergence of JEV occurrences. Some murine models elucidate the immunological phenomena of JEV infections, the more detailed pathogenesis depending on the genetic variation is yet to be well defined. And the immune-epidemiological traits also address significant concerns regarding the effective vaccines and immunotherapeutics against JEV infections. Therefore, we summarized some critical notions on molecular epidemiology, immunogenicity, and genetic variance of JEV in South-East Asia.