RNA-Seq analysis of peripheral blood mononuclear cells reveals unique transcriptional signatures associated with disease progression in dengue patients

Banerjee, Arup; Shukla, Shweta; Pandey, AK; Goswami, Saptamita; Bandyopadhyay, Bhaswati; Ramachandran, V G; Das, Shukla; Malhotra, Arjun; Agarwal, Amitesh; Adhikari, Satyabrata; Rahman, Mustafizur; Chatterjee, Shatakshee; Bhattacharya, Nemai; Basu, Nandita; Pandey, Priyanka; Sood, Vikas; Vrati, Sudhanshu

doi:10.1016/j.trsl.2017.06.007

Cited by 37 publications

(35 citation statements)

References 36 publications

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“…These two important genes play a vital role in DENV replication and antiviral response. In our previous study (20), we observed a significant decrease in the CUL3 transcripts in the PBMCs of the DS patients. In DENV-infected THP1 cells, CUL3 levels decreased significantly in a time-dependent manner (Fig.…”

Section: Figmentioning

confidence: 60%

“…It was approved by the Ethics Committee of School of Tropical Medicine (STM) Kolkata and Guru Teg Bahadur (GTB) Hospital, Delhi. All these samples were collected during 2014 to 2016, as described earlier (20). Written consent was obtained from each participant.…”

Section: Methodsmentioning

confidence: 99%

“…The integrated list generated, consisting of 6,416 genes with the validated status or a minimum of three hits from miRSystem, had 89 commonly dysregulated miRNAs in all dengue patients. We compared the predicted target 6,416 genes against the 336 genes significantly altered in the PBMCs of the dengue patients in our previous study (20). A total of 77 of the previously reported dengue infection-associated genes (20) were found to be targeted by these differentially expressed miRNAs (Table S3).…”

Section: Figmentioning

confidence: 99%

“…We compared the predicted target 6,416 genes against the 336 genes significantly altered in the PBMCs of the dengue patients in our previous study (20). A total of 77 of the previously reported dengue infection-associated genes (20) were found to be targeted by these differentially expressed miRNAs (Table S3). Further narrowing identified 12 genes that were significantly altered in the DI, DWS, and DS groups, and their expressions were negatively correlated with the expression of miRNAs, suggesting a potential target for these miRNAs (Table S4).…”

Section: Figmentioning

confidence: 99%

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High-Throughput RNA Sequencing Analysis of Plasma Samples Reveals Circulating microRNA Signatures with Biomarker Potential in Dengue Disease Progression

Saini

Bandyopadhyay²,

Pandey

et al. 2020

mSystems

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The circulating microRNA (miRNA) profile has been widely used for identifying potential biomarkers against viral infections. However, data on circulating microRNA expression patterns in dengue patients are scanty. Considering the impact of severity caused by dengue infection, circulating miRNA profiles in plasma of dengue patients may prove to be valuable for developing early prognostic markers for the disease severity. Here, we described an in-depth analytical study of small RNA sequencing data obtained from the plasma of 39 dengue patients. Integrating bioinformatics and in vitro studies, we identified differentially expressed miRNAs (DEMs) (log2 fold change ≥1.5, P < 0.05) associated with dengue disease progression. In comparing miRNA expression pattern with the follow-up samples, nine miRNAs were found to exhibit an altered expression that could distinguish between severe dengue and the convalescent patients. To understand the abundance and specificity of the DEMs in the context of dengue infection and disease progression, eight top-hit DEMs were further validated in the dengue virus-infected cell lines as well as in the patient’s plasma and peripheral blood mononuclear cells (PBMCs) using the quantitative reverse transcription-PCR (qRT‐PCR) method. Importantly, receiver operating curve analysis further confirmed that the plasma expression pattern of hsa-miR-122-5p could differentiate between different stages of dengue infection (area under the concentration-time curve [AUC] = 0.792), and dengue-negative patients with other febrile illnesses (AUC = 0.984). The in silico analysis of DEM target genes suggested an enrichment of the pathways associated with metabolism and inflammation. Our study gives a global view of miRNA expression in the plasma from dengue patients and provides a precious resource of candidate miRNAs involved in dengue infection and disease progression. IMPORTANCE Dengue virus (DENV) infection usually causes dengue fever (DF) with flu-like illness affecting infants, young children, and adults. The DF occasionally evolves into a potentially lethal complication called dengue severe (DS) leading to a rapid fall in platelet count along with plasma leakage, fluid accumulation, respiratory distress, and severe bleeding. The diverse clinical spectrum of dengue disease, as well as its significant similarity to other febrile viral illnesses, makes early identification more challenging in this high-risk group. microRNAs (miRNAs) are small (∼19 to 21 nucleotides [nt] in length), noncoding RNAs, extremely stable and easily detectable in the plasma; thus, they have potential as biomarkers for diagnosing and monitoring human diseases. This study provides a comprehensive analysis of miRNAs circulating in plasma of dengue virus-infected patients and identifies the miRNA signatures that have biomarker potential for dengue infection and disease progression.

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Section: Figmentioning

confidence: 60%

Section: Methodsmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

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High-Throughput RNA Sequencing Analysis of Plasma Samples Reveals Circulating microRNA Signatures with Biomarker Potential in Dengue Disease Progression

Saini

Bandyopadhyay²,

Pandey

et al. 2020

mSystems

Self Cite

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“…Peripheral blood mononuclear cells (PBMC) has been reported to be susceptible to DENV infection and display a vigorous cytokine/chemokine response upon viral infection [16–18]. Variable profiles of cytokines/chemokines gene expression were also observed in patients during phases of dengue illness [9].…”

Section: Introductionmentioning

confidence: 99%

Inhibitory Effect of Alpha-Mangostin to Dengue Virus Replication and Cytokines Expression in Human Peripheral Blood Mononuclear Cells

Sugiyanto

Yohan

Hadisaputro

et al. 2019

Nat. Prod. Bioprospect.

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Massive pro-inflammatory cytokines production has been correlated with the pathogenesis of severe dengue disease. The active compound of mangosteen fruit pericarps, α-mangostin, has been commonly used as traditional medicine and dietary supplement. We examined the effect of α-mangostin against dengue virus (DENV) infection in human peripheral blood mononuclear cells (PBMC) by the measurement of virus titer and TNF-α and IFN-γ cytokines concentration post infection. Increasing concentration of α-mangostin inhibited virus replication and reduced inflammatory cytokines expression at 24- and 48-h post infection. Our results support the potential use of α-mangostin as anti-antiviral and anti-inflammatory therapies in the treatment of dengue.Graphic Abstract

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Monocarboxylic Acid Transporters

Morris¹,

Kwatra²

2022

Drug Transporters

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RNA-Seq analysis of peripheral blood mononuclear cells reveals unique transcriptional signatures associated with disease progression in dengue patients

Cited by 37 publications

References 36 publications

High-Throughput RNA Sequencing Analysis of Plasma Samples Reveals Circulating microRNA Signatures with Biomarker Potential in Dengue Disease Progression

High-Throughput RNA Sequencing Analysis of Plasma Samples Reveals Circulating microRNA Signatures with Biomarker Potential in Dengue Disease Progression

Inhibitory Effect of Alpha-Mangostin to Dengue Virus Replication and Cytokines Expression in Human Peripheral Blood Mononuclear Cells

Monocarboxylic Acid Transporters

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