Virus-host Interactions in Early Japanese Encephalitis Virus Infection

Abstract

Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic virus that can cause severe viral encephalitis. Initial interactions between JEV and host cells are required for productive viral infection and initiation of the viral life cycle. The elucidation of these interactions is critical, not only to understand the pathogenesis of JEV infection, but also to design efficient antiviral strategies. In this review, we outline the known viral and cellular components involved in JEV entry into host cells, with a particular focus on the initial virus-host cell interaction on the cell surface and the downstream early events such as endocytosis, membrane fusion, and viral genome release.

Keywords: Endocytosis mechanism; Japanese encephalitis virus; Membrane fusion; Putative receptor; Viral entry.

Fig. 1

A model of JEV entry routes. After binding to putative receptors on the cell surface, JEV enters cells through different endocytosis pathways in different cell types. (A) Clathrin-mediated endocytosis depends on dynamin and plays an important role in JEV entry into some non-neural cells; (B) Caveolin-mediated endocytosis. JEV enters some neural cells via caveolin-1, cholesterol and dynamin-2-mediated endocytosis. After binding to neuronal cells, JEV activates the EGFR-PI3K-RhoA signaling pathway, which may promote the phosphorylation of caveolin-1 and its aggregation on the cell membrane by regulating the actin cytoskeleton rearrangement, following the phosphorylated caveolin-1 activates Rac1, which then enables JEV to penetrate cells through caveolin-1-mediated endocytosis.