The hidden threats posed by Japanese encephalitis virus genotype V

TL;DR

Japanese encephalitis virus genotype V is emerging as a threat due to its distinct characteristics and potential resistance to current vaccines.

Contribution

This review highlights the unique properties of genotype V and questions the adequacy of current vaccines against it.

Findings

Genotype V JEV is predominant in Korean mosquitoes and shows higher lethality in animal studies.

Current vaccines based on genotype III offer insufficient protection against genotype V.

Breakthrough infections and potential impact on control strategies are documented.

Abstract

Japanese encephalitis virus (JEV) remains a major cause of viral encephalitis in Asia. Among its five genotypes (GI–GV), genotype V (GV) has re-emerged and become the predominant lineage in mosquitoes in the Republic of Korea, with sporadic human cases also reported. GV JEV displays differences from other genotypes in genomic sequence, antigenicity, and pathogenicity, and animal studies indicate higher lethality. Importantly, all currently used vaccines are based on GIII strains and provide partial but insufficient protection against GV JEV, with breakthrough infections documented. These findings raise concerns that GV circulation could undermine existing control strategies. Although shifts in mosquito vectors have been observed, the broader epidemiological and clinical impact of GV JEV remains poorly defined. In the absence of specific antiviral therapies, systematic evaluation is needed to determine whether GV-based vaccines are warranted. This review summarizes current evidence on the epidemiology, molecular and biological characteristics, and vaccine protection of GV JEV, and highlights priorities for surveillance and future research.

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