Insight into SNPs and epitopes of E protein of newly emerged genotype-I isolates of JEV from Midnapur, West Bengal, India

Abstract

BackgroundJapanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes Japanese Encephalitis (JE) and Acute Encephalitis Syndrome (AES) in humans. Genotype-I (as co-circulating cases with Genotype-III) was isolated in 2010 (JEV28, JEV21) and then in 2011 (JEV45) from Midnapur district, West Bengal (WB) for the first time from clinical patients who were previously been vaccinated with live attenuated SA14-14-2 strain. We apply bioinformatics and immunoinformatics on sequence and structure of E protein for analysis of crucial substitutions that might cause the genotypic transition, affecting proteinfunction and altering specificity of epitopes.ResultsAlthough frequency of substitutions in E glycoprotein of JEV28, JEV21 and JEV45 isolates vary, its homologous patterns remain exactly similar as earlier Japan isolate (Ishikawa). Sequence and 3D model-structure based analyses of E protein show that only four of all substitutions are critical for genotype-I specific effect of which N103K is common among all isolates indicating its role in the transition of genotype-III to genotype-I. Predicted B-cell and T-cell epitopes are seen to harbor these critical substitutions that affect overall conformational stability of the protein. These epitopes were subjected to conservation analyses using a large set of the protein from Asian continent.ConclusionsThe study identifies crucial substitutions that contribute to the emergence of genotype-I. Predicted epitopes harboring these substitutions may alter specificity which might be the reason of reported failure of vaccine. Conservation analysis of these epitopes would be useful for design of genotype-I specific vaccine.Electronic supplementary materialThe online version of this article (doi:10.1186/s12865-017-0197-9) contains supplementary material, which is available to authorized users.

Full-Length Genome Sequence of Japanese Encephalitis Virus Strain FC792, Isolated from Guangxi, China

“…JEV infection can cause abortion or stillbirth in pregnant sows, piglets that are mummified or weak at birth, boar orchitis, etc., leading to great economic losses to pig-raising industries ( 4 ). JEV infection can also lead to acute encephalitis in humans; approximately 25 to 30% of JEV cases are fatal, and 50% result in permanent neuropsychiatric sequelae ( 5 , 6 ).…”

Insight into the Salt Bridge of Malate Dehydrogenase from Halobacterium salinarum and Escherichia coli

“…The details of development of the model of hsMDH against the template (4BGU), minimization and evaluation are performed as earlier [24, 25, 26, 27, 28, 29]. The main chain dihedral angles (Φ and Ψ) are seen to occupy the favored region of the Ramachandran plot (Figure 1a,b).…”

“…To date there are 10 structures of malate dehydrogenase from Haloacrula marismortui (hmMDH; 9) and Haloferax volcanii (hvMDH; 1) in RCSB, PDB database. The model of hsMDH (UniProt ID: Q9HMV8) is developed against the template structure of hvMDH (PDB ID: 4BGU; UniProt ID: Q9P9L2) using Modeller 9v11 in-built scripts as earlier [24, 25, 26, 27, 28, 29]. Use of the latter structure as template over the structures of hmMDH is justified as hvMDH has 83% sequence identity (which is 6% higher than hmMDH) with hsMDH and that the crystal structure of hvMDH, 4BGU has highest resolution (1.5 Å) of any known crystal structure of halophilic malate dehydrogenases in the database.…”

“…Use of the latter structure as template over the structures of hmMDH is justified as hvMDH has 83% sequence identity (which is 6% higher than hmMDH) with hsMDH and that the crystal structure of hvMDH, 4BGU has highest resolution (1.5 Å) of any known crystal structure of halophilic malate dehydrogenases in the database. Alignment between the template (4BGU_A, 303 amino acids) and the target (Q9HMV8, 304 amino acids) was performed as earlier [24, 25,26] along with manual improvements [24, 25, 27, 30]. Final model was selected based on the Discrete Optimized Protein Energy (DOPE) score.…”

“…The model was refined using AUTOMINv1.0 [31]. Final model was evaluated as earlier [24, 26, 27, 28, 29] along with ion-pairs [25].…”