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Molecular pathogenesis of Japanese encephalitis and possible therapeutic strategies.

ABSTRACT: Japanese encephalitis virus (JEV), a single-stranded, enveloped RNA virus, is a health concern across Asian countries, associated with severe neurological disorders, especially in children. Primarily, pigs, bats, and birds are the natural hosts for JEV, but humans are infected incidentally. JEV requires a few host proteins for its entry and replication inside the mammalian host cell. The endoplasmic reticulum (ER) plays a significant role in JEV genome replication and assembly. During this process, the ER undergoes stress due to its remodelling and accumulation of viral particles and unfolded proteins, leading to an unfolded protein response (UPR). Here, we review the overall strategy used by JEV to infect the host cell and various cytopathic effects caused by JEV infection. We also highlight the role of JEV structural proteins (SPs) and non-structural proteins (NSPs) at various stages of the JEV life cycle that are involved in up- and downregulation of different host proteins and are potentially relevant for developing efficient therapeutic drugs.

SUBMITTER: Kumar S

PROVIDER: S-EPMC9162114 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionJapanese encephalitis (JE) is a mosquito-borne viral infection of the brain that can cause permanent brain damage and death. In the Philippines, efforts are underway to deliver a live attenuated JE vaccine (CD-JEV) to children under five years of age (YOA), who are disproportionately infected. Multiple vaccination strategies are being considered.MethodsWe conducted a cost-effectiveness analysis comparing three vaccination strategies to the current state of no vaccination from the societal and government perspectives: (1) national routine vaccination only, (2) sub-national campaign followed by national routine, and (3) national campaign followed by national routine. We developed a Markov model to estimate impact of vaccination or no vaccination over the child's lifetime horizon, assuming an annual incidence of 10.6 cases per 100,000. Costs of illness ($859/case), vaccine ($0.50/dose), routine vaccination ($0.95/dose), and campaign vaccination ($0.98/dose) were based on hospital financial records, expert opinion and literature. The societal perspective included transportation and opportunity costs of caregiver time, in addition to costs incurred by the health system.ResultsJE vaccination via national campaign followed by national routine delivery was the most cost-effective strategy modeled with a cost per disability adjusted life year (DALY) averted of $233 and $29 from the government and societal perspectives, respectively. Results were similar for other delivery strategies with cost/DALY ranging from $233 to $265 from the government perspective and $29-$57 from the societal perspective. JE vaccination was projected to prevent 27,856-37,277 cases, 5571-7455 deaths, and 173,233-230,704 DALYs among children under five over 20 consecutive birth cohorts. Total incremental costs of vaccination versus no vaccination over 20 birth cohorts were $6.6-$9.8 million from the societal perspective ($230 K-$440 K annually) and $45.9-$53.9 million ($2.2 M-$2.7 M annually) from the governmental perspective.ConclusionVaccination with CD-JEV in the Philippines is projected to be cost-effective, reducing long-term costs associated with JE illness and improving health outcomes compared to no vaccination.

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Molecular pathogenesis of Japanese encephalitis and possible therapeutic strategies.

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