Japanese Encephalitis Virus and Host Innate Immunity: Insights Into TLR Signaling, PRR Crosstalk, and Viral Immune Evasion

Abstract

Japanese encephalitis virus (JEV), a neurotropic flavivirus and a major cause of viral encephalitis, poses a significant global health threat due to its neuroinvasive potential. Host innate immune responses, particularly those mediated by pattern-recognition receptors such as Toll-like receptors (TLRs) and RIG-I–like receptors, play critical roles in detecting JEV infection in neurons and glial cells, triggering antiviral defenses through induction of type I interferons (IFNs), inflammatory cytokines, and interferon-stimulated genes. However, dysregulated inflammatory responses may contribute to neurodegeneration and disease severity. JEV has evolved multiple immune evasion strategies, including suppression of IFN signaling, modulation of host microRNAs, and exploitation of cellular pathways such as autophagy to facilitate viral replication and persistence. This review summarizes current knowledge regarding TLR and other PRRs-mediated innate immune sensing during JEV infection, highlights the molecular mechanisms underlying viral immune evasion, and discusses the potential of TLR agonists as antiviral immunomodulators and vaccine adjuvants.