Does Japanese encephalitis virus share the same cellular receptor with other mosquito-borne flaviviruses on the C6/36 mosquito cells?

Abstract

Japanese encephalitis virus (JEV) is a member of mosquito-borne Flaviviridae. To date, the mechanisms of the early events of JEV infection remain poorly understood, and the cellular receptors are unidentified. There are evidences that the structure of the virus attachment proteins (VAP), envelope glycoprotein of mosquito-borne flaviviruses is very similar, and the vector-virus interaction of mosquito-borne flaviviruses is also very similar. Based on the studies previously demonstrated that the similar molecules present on the mosquito cells involved in the uptake process of JEV, West Nile virus (WNV) and Dengue virus (DV), it is proposed that the same receptor molecules for mosquito-borne flaviviruses (JEV, WNV and DV) may present on the surface of C6/36 mosquito cells. By co-immunoprecipitation assay, we investigated a 74-KDa protein on the C6/36 cells binds JEV, and the mass spectrometry results indicated it may be heat shock cognate protein 70(HSC70) from Aedes aegypti. Based upon some other viruses use of heat shock protein 70 (HSP70) family proteins as cell receptors, its possible HSC70's involvement in the fusion of the JEV E protein with the C6/36 cells membrane, and known form of cation channels in the interaction of HSC70 with the lipid bilayer, it will further be proposed that HSC70 as a penetration receptor mediates JEV entry into C6/36 cells.

Figure 1

Summary of the Structural Organization and Different Conformations of the Flavivirus Envelope Protein E (obtained the kind permission from the copyright holder to reproduce figures that have previously been published on [51]). (A) Schematic top view of the organization of the sE protein dimer as present at the surface of mature virions, color-coded according to the three domains (DI, DII, and DIII). The fusion peptide (FP) is indicated in orange. (B) Crystal structure (top view) of the TBEV E ectodomain (termed "sE") dimer. (C) Schematic side view of the DV E dimer at the surface of mature virions, with the "stem" and TM C-terminal polypeptide segments (missing in the truncated sE form) indicated in green. The viral lipid bilayer is illustrated with lipids belonging to the outer and inner leaflets colored blue and pink, respectively. Cryo-electron microscopy 3D reconstructions have shown that the stem forms two α-helices (H1 and H2) lying on the viral membrane, followed by the two transmembrane (TM) segments. (D) Schematic representation illustrating the proposed organization of full-length DV E in its postfusion conformation. In this model, the α-helices of the stem interact with the body of the trimer, in the grooves between adjacent, parallel DIIs. The lipid bilayer as well as the stem and TM segments is drawn as in (C).