microRNA expression profiling and bioinformatic analysis of dengue virus-infected peripheral blood mononuclear cells

Abstract

Abstract. Dengue virus (DENV) causes self-limiting dengue fever (DF), severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). It is generally considered that cytokine storm leads to the increased plasma leakage characteristic of DHF/DSS. In the present study, peripheral blood mononuclear cells (PBMCs) were isolated from blood samples of healthy volunteers and infected with DENV serotype 2 (DENV2). Culture supernatants of DENV2-infected and -uninfected PBMCs were analyzed using a human cytokine array. Between a 6-12 h post-infection, levels of CCL5, IL-6 and IL-8 were markedly elevated, while those of TNF-α decreased. Total RNA isolated from these PBMCs was analyzed by human miRNA microarray to identify differentially expressed microRNAs (miRNAs). Quantitative reverse transcription polymerase chain reaction was used to validate 11 upregulated and 4 downregulated miRNAs. Sanger mibase, miRanda and TargetScan were used to identify 261 common predicted genes. Databases were used to identify homologous sequences on mRNAs of putative target genes that may be directly bound by the miRNAs identified. We found that cytokines and epigenetic regulators may be putative target genes of these miRNAs. Using ingenuity pathway analysis, we noted that canonical pathways, including biological regulation, may be modulated by these miRNAs.

The miRNA world of polyomaviruses

“…It will be of particular interest to see whether miRNA profiling studies where infected and non-infected cells are compared, reveal new host miRNAs affected by a specific polyomavirus. Similar studies with other viruses have demonstrated that this might be a successful approach to identify new host miRNAs involved in viral infection [91-94]. …”

Human MicroRNA miR-532-5p Exhibits Antiviral Activity against West Nile Virus via Suppression of Host Genes SESTD1 and TAB3 Required for Virus Replication

“…Dengue virus (DENV) infection was shown to alter the expression of numerous miRNAs in mosquito (18) and human (19) cells. In particular, DENV strongly induced the expression of miR-146a in human monocytes, with significant benefit to virus replication (20).…”

Let‐7e inhibits TNF‐α expression by targeting the methyl transferase EZH2 in DENV2‐infected THP‐1 cells

“…Researchers have demonstrated significantly increased TNFα plasma levels in DHF/DSS patients compared with those in DF patients (Green et al, ). A study by our group also found that TNFα was up‐regulated in DENV2‐infected peripheral blood mononuclear cells (PBMCs) (Qi et al, ). Sam et al () found that high TNFα secretion was likely to protect patients from severe dengue by inhibiting DENV replication during the early infection phase.…”

“…TNFα is involved in clearing viruses and the host immune defense in the infection processes of various viruses, such as West Nile virus (Shrestha, Zhang, Purtha, Klein, & Diamond, ), encephalomyocarditis virus (Wada et al, ), hepatitis B virus (Kim et al, ), and influenza virus (Seo & Webster, ). Accumulating evidence indicates that TNFα plays an important role in the occurrence and development of DENV infection (Green et al, ; Lim et al, ; Qi, Li, Zhang, & Huang, ; Sam, Omar, Teoh, Abd‐Jamil, & AbuBakar, ; Sam, Teoh, Chinna, & AbuBakar, ). The relationship between severe or fatal dengue‐related clinical features and cytokine gene polymorphisms was confirmed (Sam et al, ).…”