Changes in circulating microRNAs (miRNAs) in the cerebrospinal fluid (CSF) have been associated with different neurological diseases. Here, we presented results of a pilot study aimed at determining the feasibility of detecting miRNAs in the CSF of Japanese Encephalitis virus (JEV) infected individuals with acute encephalitis syndrome (AES). We demonstrated the circulating miRNA profile in CSF of acute encephalitis patients infected with JEV. Using a quantitative real-time PCR-based miRNA array, we examined the level of 87 miRNAs expressed in human exosomes isolated from CSF. Subsequently, correlation between cytokine level and miRNAs expression in CSF samples was examined. In this study, we identified and validated the upregulated expression of three miRNAs, miR-21-5p, miR-150-5p, and miR-342-3p that were specifically circulated in CSF of acute encephalitis patients infected with JEV. CSF miR-21-5p, miR-150-5p, and miR-342-3p expressions were also elevated in infected mice brain. However, the expression pattern of these miRNAs differed in neuronal cells, microglial cells, and the exosome derived from JEV-infected cell culture supernatant. Interestingly, neuronal cells infected with vaccine strain (SA-14-14) did not lead to any upregulation of these three miRNAs. Further, miR-150-5p expression was found to be negatively correlated(r = -0.5279, p = 0.016) with TNFα level. Pathway analysis of putative target genes of these miRNAs indicated involvement of TGF-β, NGF, axon guidance, and MAPK signaling pathways in JEV/AES patients. This study for the first time represents the circulating miRNA in CSF of AES patients and identified the upregulated miRNAs in JEV-infected patients and offers the basis for future investigation.
Dengue is a rapidly emerging and re-emerging mosquito-borne disease and a serious burden on Indian population. Recombination, selection
pressure may play a major role in dengue virus (DENV) evolution. The present study describes the evolutionary time-scale of dengue virus
serotype 2 and 4 strains along with its recombination study and selection pressure analysis in Kolkata, Eastern India. Sequencing of the CapsidPremembrane-Envelop (C-prM-E) region was performed in DENV2 and 4 strains. Maximum likelihood tree was constructed using MEGA
softwere. Bayesian phylogenetic analysis was done using best-t model for each dataset. Recombination and selection pressure on structural genes
was determined using Datamonkey online platform and RDP4 software. All DENV2 strains were grouped with cosmopolitan genotype and all
DENV4 strains were clustered with Genotype I. Mutations at the B and T cell epitopes were revealed. Nucleotide substitution rate of DENV2: 7.49
×10−4 substitutions/site/year and DENV4: 6.79 × 10-4 substitutions/site/year. Time to the most recent common ancestor of DENV2 and DENV4
viruses was 185 years and 190 years respectively. STM20039/14 was a recombination product of GWL-18-INDI-01 strain and STM20758A/16
ancestor strains. Selection pressure analysis revealed that purifying negative selection was the major driving force. This is the rst report of
recombination in DENV2 Cosmopolitan genotype in India. Also, we are reporting for the rst time about the genetic and evolutionary
characteristics of DENV4 strains from Eastern India. This study will be useful for the continuous surveillance of disease burden, viral
epidemiology to take proper measures for disease control.
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