Transient receptor potential channels in Flaviviridae infection: A comprehensive review

Diseases caused by Flaviviridae viruses exert profound global health and economic burdens due to their high incidence and associated mortality. Infection by the Flaviviridae family often leads to severe acute or chronic illnesses, including hemorrhagic systemic diseases caused by dengue virus (DENV) and yellow fever virus, neurological complications associated with West Nile virus and Zika virus (ZIKV) infection, as well as liver damage and hepatocellular carcinoma resulting from hepatitis C virus (HCV) infection. Accumulating evidence indicates that a hallmark of Flaviviridae infection is to hijack calcium (Ca²⁺) signaling of the host cells, consequently facilitating viral entry, RNA replication, viral assembly, and release. Transient receptor potential (TRP) channels, a superfamily of nonselective cation channels, are central regulators of intracellular Ca²⁺ homeostasis. Recent studies reveal that TRP channels are closely involved in Flaviviridae infection. This comprehensive review synthesizes current findings on the role of TRP channels (e.g. TRPC, TRPV, TRPA, TRPM, and TRPML) in the pathogenesis of Flaviviridae viruses such as DENV, ZIKV, HCV, and Japanese encephalitis virus. Moreover, this review summarizes virus-TRP channel interaction mechanisms and discusses the potential of targeting TRP channels for host-directed antiviral therapies. This review aims to establish a conceptual framework for understanding TRP channel biology in Flaviviridae infection and to guide future research on antiviral strategies. Future directions should highlight the potential utility of TRP channel research for advancing anti-Flaviviridae therapies and clarifying their underlying mechanisms.