Abstract
This paper highlights various reasons of evolution of new mutants/variants of JE virus and its effects on neurovirulence, antigenicity, host immune responses, and disease transmission in endemic areas. Virus is reorganizing its genome by making sequence alterations, single site mutations, cluster specific reversions, and amino acid substitutions in neutralizing antigenic sites mainly in N′ glycosylation sites and epitopic regions of S and E proteins. Virus is regularly changing gene order, gene density by making substitution point mutations in important structural genes which make virus envelope proteins. Further, JE virus acquiring new genetic variations and adaptabilities through genetic recombination of wild strains with vaccine strains and assimilating new lethal genes that lead to emergence of molecular variants/mutants. These newly emerged JE virus genotypes have attained the ability to escape the immune defense and show wider resistance against vaccines and therapeutic agents. Thus new strains did significant elevation in the level of neurovirulence, antigenicity and pathogenesis. It is causing very high mortalities in various infant groups and imposing lifelong irreversible disorders in survivors and showing a regular trend of emergence and reemergence in endemic areas. The present review article emphasizes methods to suppress virus replication, reversion of neurovirulence, attenuation and an utmost need of more potential vaccines against cross reactive heterologous genotypes of JE virus to control disease transmission and mortalities occurring in endemic areas.
Highlights
Flavivirus, Japanese encephalitis (JE) virus, is the leading cause of acute viral encephalitis syndrome of central nervous system and mortalities of patients throughout Asia [1]
Vaccine strains of many viruses like rabies [7], West Nile Virus [8], Vaccinia virus [9], Influenza [10], Yellow fever virus [1], and JE virus [11] are acquiring similar changes in genome and developing new mutant forms which are antibody resistant and environmentally adapted. These environmentally adapted new variants/mutants are proved to be more lethal than normal strains because of production of high neurovirulence and pathogenesis in human hosts mainly in various infant groups
From studies, it is clear that single site mutations and ecoclimatic, demographic, and clinical reasons are responsible for advent of new antibody resistant JE virus strains in endemic areas
Summary
Flavivirus, Japanese encephalitis (JE) virus, is the leading cause of acute viral encephalitis syndrome of central nervous system and mortalities of patients throughout Asia [1]. Vaccine strains of many viruses like rabies [7], West Nile Virus [8], Vaccinia virus [9], Influenza [10], Yellow fever virus [1], and JE virus [11] are acquiring similar changes in genome and developing new mutant forms which are antibody resistant and environmentally adapted These environmentally adapted new variants/mutants are proved to be more lethal than normal strains because of production of high neurovirulence and pathogenesis in human hosts mainly in various infant groups. From studies, it is clear that single site mutations and ecoclimatic, demographic, and clinical reasons are responsible for advent of new antibody resistant JE virus strains in endemic areas These are considered as real cause of endemic expansion, disease transmission, and prevalence of Japanese encephalitis virus. In the present paper, all possible reasons of enhancement of neurovirulence, antigenicity, host immune responses, and transmission of JE have been discussed with the due emphasis on development of most appropriate and potential vaccine
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