MicroRNA profiling of mouse liver in response to DENV-1 infection by deep sequencing

• Published in: PeerJ (San Francisco, CA) CA), 2019-04, Vol.7, p.e6697, Article e6697
• Main Authors: Pong, Lian Yih, Parkkinen, Sinikka, Dhanoa, Amreeta, Gan, Han Ming, Wickremesinghe, Indeevari Abisheka Chiharu, Syed Hassan, Sharifah
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Adaptive immunity; AKT protein; Analysis; Bioinformatics; Bone morphogenetic proteins; Dengue fever; Dengue virus; Gene expression; Genes; Genetic research; Genomics; Growth factors; Health aspects; Host-virus interaction; Immune response; Immunology; Infection; Infections; Infectious Diseases; Intracellular miRNA; Kinases; Liver; MAP kinase; Medical research; MicroRNA; MicroRNAs; miRNA; MiSeq sequencing; Molecular modelling; Mosquitoes; Mouse liver; Pathogenesis; Rap1 protein; Rodents; Serotypes; Signal transduction; Small RNA; Transforming growth factor-b; Transforming growth factors; Viral diseases; Virology; Virus diseases; Viruses; Wnt protein
• ISSN: 2167-8359; 2167-8359
• DOI: 10.7717/peerj.6697

Dengue caused by dengue virus (DENV) serotypes -1 to -4 is the most important mosquito-borne viral disease in the tropical and sub-tropical countries worldwide. Yet many of the pathophysiological mechanisms of host responses during DENV infection remain largely unknown and incompletely understood. Using a mouse model, the miRNA expressions in liver during DENV-1 infection was investigated using high throughput miRNA sequencing. The differential expressions of miRNAs were then validated by qPCR, followed by target genes prediction. The identified miRNA targets were subjected to gene ontology (GO) annotation and pathway enrichment analysis to elucidate the potential biological pathways and molecular mechanisms associated with DENV-1 infection. A total of 224 and 372 miRNAs out of 433 known mouse miRNAs were detected in the livers of DENV-1-infected and uninfected mice, respectively; of these, 207 miRNAs were present in both libraries. The miR-148a-3p and miR-122-5p were the two most abundant miRNAs in both groups. Thirty-one miRNAs were found to have at least 2-fold change in upregulation or downregulation, in which seven miRNAs were upregulated and 24 miRNAs were downregulated in the DENV-1-infected mouse livers. The miR-1a-3p was found to be the most downregulated miRNA in the DENV-1-infected mouse livers, with a significant fold change of 0.10. To validate the miRNA sequencing result, the expression pattern of 12 miRNAs, which were highly differentially expressed or most abundant, were assessed by qPCR and nine of them correlated positively with the one observed in deep sequencing. functional analysis revealed that the adaptive immune responses involving TGF-beta, MAPK, PI3K-Akt, Rap1, Wnt and Ras signalling pathways were modulated collectively by 23 highly differentially expressed miRNAs during DENV-1 infection. This study provides the first insight into the global miRNA expressions of mouse livers in response to DENV-1 infection and the possible roles of miRNAs in modulating the adaptive immune responses during DENV-1 infection.