Homology models have been developed for two Indian strains of the JEV envelope glycoprotein viz. Bankura and Vellore, using the 2.4 Angstrom , dimeric, Dengue Type 2 envelope protein crystallographic structure (1OKE.PDB) as a template. Molecular dynamics (MD) simulations and energy minimization was carried out to obtain energetically stable structures. The mutation E138K in the Bankura strain was found to be a part of the antigenic determinant and resulted in change of the surface charge distribution from negative to positive (Fig). This may be responsible for inhibition of protein binding to the cell membrane and subsequent loss of virulence of the virus. In case of the Vellore strain, the mutation G153W which is near the glycosylation site Asn154, on MD annealing, changed the conformation of the residues Glu150 and Asn151 to a 310 helix (Fig). This conformational change may in turn be responsible for affecting the glycosylation process. Further, the glycosylation site was found to be in the mapped conformational epitopes. This could explain reports in other flaviviruses of attenuation, due to glycosylation site mutations.
The mutation E138K as a part of the antigenic determinant may be responsible for inhibition of protein binding to the cell membrane. In addition, the observation that the glycosylation site is also in the mapped epitopes explains reports in other flaviviruses of attenuation, due to glycosylation site mutations.
PrabhakarG, Sarah Cherian, C. Dayaraj, “In Silico sequence and structure based antigenic analysis of the envelope glycoprotein of two Indian strains (Bankura & Vellore) of Japanese Encephalitis Virus” at the Asia-Pacific Congress of Medical Virology, Delhi. (Nov 13-15, 2006).
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