Dynamic changes in global microRNAome and transcriptome reveal complex miRNA-mRNA regulated host response to Japanese Encephalitis Virus in microglial cells.

Microglia cells in the brain play essential role during Japanese Encephalitis Virus (JEV) infection and may lead to change in microRNA (miRNA) and mRNA profile. These changes may together control disease outcome. Using Affymetrix microarray platform, we profiled cellular miRNA and mRNA expression at multiple time points during viral infection in human microglial (CHME3) cells. In silico analysis of microarray data revealed a phased pattern of miRNAs expression, associated with JEV replication and provided unique signatures of infection. Target prediction and pathway enrichment analysis identified anti correlation between differentially expressed miRNA and the gene expression at multiple time point which ultimately affected diverse signaling pathways including Notch signaling pathways in microglia. Activation of Notch pathway during JEV infection was demonstrated in vitro and in vivo. The expression of a subset of miRNAs that target multiple genes in Notch signaling pathways were suppressed and their overexpression could affect JEV induced immune response. Further analysis provided evidence for the possible presence of cellular competing endogenous RNA (ceRNA) associated with innate immune response. Collectively, our data provide a uniquely comprehensive view of the changes in the host miRNAs induced by JEV during cellular infection and identify Notch pathway in modulating microglia mediated inflammation.

A novel peptide interferes with Mycobacterium tuberculosis virulence and survival.

Tuberculosis (TB) is a huge global burden, with new and resistant strains emerging at an alarming rate, necessitating an urgent need for a new class of drug candidates. Here, we report that SL3, a novel 33-amino acid peptide, causes debilitating effects on mycobacterial morphology. Treatment with SL3 drastically inhibits the growth of Mycobacterium tuberculosis in vitro as well as in a pre-clinical mouse model for M.tb infection. Microarray analysis of SL3-expressing strain demonstrates wide-scale transcriptional disruption in M.tb. We therefore believe that SL3 and similar peptides may herald a new approach towards discovering new molecules for TB therapy.

Phylogenetic analysis of poly and non structural protein in Japanese Encephalitis virus with other related viral families.

BACKGROUND: Japanese encephalitis (JE) causes inflammation of brain. The mortality rate due to JE is 30% while 10 -15 % of patients make full recovery. The disease spreads through infected mosquito bites breeding in rice fields and feeds on pigs, birds, and ducks. PURPOSE: As proteins show important structure to function relationship the study was designed to carry out the identification of poly and non-structural proteins in the infective virus group using different strains of Japanese encephalitis virus i.e. JAOARS982, Nakayama Strain SA (V), Strain SA-14. METHODS: With reference to non structural proteins we obtained protein sequences of the following Japanese encephalitis virus groups: Japanese encephalitis virus, Weatnile virus, Kunjin virus. Further comparative and phylogenetic analysis was performed to explore evolutionary relationship among these groups. RESULTS: Results of phylogeny of alignment score was found to be 375184 using multiple alignment, Jal view, ClustalW (1.83) and ClustalW2. However, the analysis among the non-structural proteins of Japanese Encephalitis Virus, Westnile Virus, and Kunjin Virus revealed the phylogeny alignment score to be 875 through multiple sequence alignment and Tree view respectively. CONCLUSION: Phylogenetic analysis revealed that these four strains are interrelated as well as showing high similarity with the other viruses of this group due to conserved regions among their sequences.

Comparative modeling of retinol-binding protein-3 and retinal S-antigen in Eales' disease and prediction of their binding sites using computational methods.

Retinal S-antigen and interphotoreceptor retinoid-binding protein-3 play a significant role in the etiopathogenesis of Eales' disease. Protein 3D structures are functionally very important and play a significant role in progression of the disease, hence these 3D structures are better target for further drug designing and relative studies. We developed 3D model structure of retinol-binding protein-3 and retinal S-antigen protein of human involved in Eales' disease. Functional site prediction is a very important and related step; hence, in the current course of analysis, we predicted putative functional site residues in the target proteins. Molecular models of these proteins of Eales' disease as documented in this study may provide a valuable aid for designing an inhibitor or better ligand against Eales' disease and could play a significant role in drug design.