"Silent messengers of chaos: unveiling the dual threat of immune infiltrates in Japanese encephalitis virus neuroinflammatory storm"

Abstract

The Japanese encephalitis virus (JEV), a neurotropic flavivirus, poses a formidable global health challenge due to its severe neurological sequelae and high lethality. Peripheral immune effectors, including monocytes, macrophages, dendritic cells, natural killer cells, and T lymphocytes, act as principal vectors of neuropathogenic exacerbation by translocating across a compromised blood-brain barrier (BBB). These cells perpetuate an inflammatory cascade within the central nervous system (CNS), characterized by unchecked cytokine dysregulation and collateral neuronal destruction. Exosomes, diminutive extracellular vesicles, emerge as cryptic propagators of JEV neuropathogenesis. Acting as molecular couriers, these vesicles disseminate viral RNA and proinflammatory mediators, thus orchestrating neuronal apoptosis and fostering a pernicious inflammatory microenvironment. Exosomal trafficking exacerbates BBB destabilization, potentiates immune cell ingress into the CNS, and establishes a deleterious feedback mechanism of neuroinflammation and cellular attrition. This review underscores the intricate crosstalk between peripheral immune infiltrates and exosomal vectors in JEV progression, advocating for advanced therapeutic paradigms aimed at intercepting exosomal biogenesis, attenuating immune hyperactivation, and preserving BBB integrity to mitigate CNS devastation.

Keywords: Japanese encephalitis virus; Blood-brain barrier dysregulation; Extracellular vesicles; Immune cell translocation.

Fig. 1

The schematic depicts the immune cell recruitment process during JEV pathogenesis, where infected monocytes serve as “Trojan horses,” accompanied by T cells. These cells traverse the disrupted BBB, fueled by JEV-triggered cytokine storms and endothelial damage, facilitating viral spread and neuroinflammation