Heat shock protein 90ß in the Vero cell membrane binds Japanese encephalitis virus

Wang, Yuan; Li, Yan; Ding, Tianbing

In viral encoded proteins, the envelope E protein on the virion surface is the most crucial protein involved in virus-host interactions, particularly during attachment to the cell receptor, virus penetration, cell tropism and virulence, as well as haemagglutination and neutralization in human protective immunity (13) . The E protein consists of 500 amino acid residues, appears as approximately 53 kDa, and is N-glycosylated (14) . An exact crystal structure of the JEV E protein ectodomain was previously produced and the major conformational properties previously suggested were confirmed based on a related flavivirus [tick borne encephalitis virus (TBEV)] E protein counterpart (15, 16) . In brief, the E protein is present on the virion surface as an anti-parallel homodimer with a convex external curvature and is anchored to the viral envelope (lipid membrane) at the distal end. Each E protein subunit is composed of 3 domains based on antigenicity (13) . Domain I is a discontinuous domain composed of 3 fragments (1-51, 137-189 and 293-311 amino acids from the amino terminal end) and is the central domain with an 8-stranded β-barrel located in the centre of the E protein molecule. Domain II is the dimerization domain on the mature virion, forms 2 loops from regions 52-136 and 190-289, projects along the virus surface between the homodimer subunit transmembrane regions, and contains a highly conserved fusion loop that likely inserts into target cell membranes (17) . Domain III (311-411) lies at the E protein C-terminus, forms a constant β-barrel composed of 7 head-to-tail β-strands, and maintains an immunoglobulin-like fold (18) . It contains the receptor-binding domain, which is connected to the central domain I by a flexible region and is a major target of neutralizing antibodies (19) .