RNA-Seq analysis of peripheral blood mononuclear cells reveals unique transcriptional signatures associated with disease progression in dengue patients
Abstract
Patients infected with Dengue virus usually present a mild, self-limiting febrile dengue infection (DI) that occasionally leads to a potentially lethal complication, called the severe dengue (DS). The ability to identify the prognostic markers of DS could allow an improved disease intervention and management. To identify the transcriptional signatures associated with the dengue disease progression, we carried out the high-throughput sequencing of the RNA isolated from the peripheral blood mononuclear cells (PBMCs) of the dengue patients of varying severity and compared with that in the patients with other febrile illnesses (OFIs) or the healthy controls. The transcriptional signatures that discriminated the DS patients from OFI and DI patients were broadly related to the pathways involving glycine, serine, and threonine metabolisms, extracellular matrix organization, ubiquitination, and cytokines and inflammatory response. Several upregulated genes in the inflammatory process (MPO, DEFA4, ELANE, AUZ1, CTSG, OLFM4, SLC16A14, and CRISP3) that were associated with the dengue disease progression are known to facilitate leukocyte-mediated migration, and neutrophil activation and degranulation process. High activity of MPO and ELANE in the plasma samples of the follow-up and recovered dengue patients, as well as and the presence of a larger amount of cell-free dsDNA in the DS patients, suggested an association of neutrophil-mediated immunity with dengue disease progression. Careful monitoring of some of these gene transcripts, and control of the activity of proteins encoded by them, may have a great translational significance for the prognosis and management of the dengue patients.
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RNA-seq of the human host can reveal new or underappreciated host-microbial interactions directly from clinical samples, as shown in Lyme disease, dengue, and malaria.
“Moreover, RNA-seq analyses of the human host can be used to identify novel or underappreciated host–microbial interactions directly from clinical samples, as previously shown for patients with Lyme disease68, dengue80 or malaria81.”
From Clinical metagenomics (2019) · cites this paper as [80]
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- Authors
- Banerjee, A., Shukla, S., Pandey, A. D., Goswami, S., Bandyopadhyay, B., Ramachandran, V., Das, S., Malhotra, A., Agarwal, A., Adhikari, S., Rahman, M., Chatterjee, S., Bhattacharya, N., Basu, N., Pandey, P., Sood, V., & Vrati, S.
- Affiliations
- Translational Health Science and Technology Institute (IN)
- University College of Medical Sciences (IN)
- School of Tropical Medicine (IN)
- National Institute of Biomedical Genomics (IN)
- Corresponding author
- Banerjee, Arup
- Vrati, Sudhanshu
- ORCID
- Venue
- Translational Research
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 186
- Pages
- 62-78.e9
- ISSN
- 1878-1810 (ISSN-L)
- 1931-5244
- OpenAlex
- W2638117886
- Cited by
- 65
- References
- 41
- Citations by year
- 2026: 13 · 2025: 8 · 2024: 7 · 2023: 13 · 2022: 9 · 2021: 5 · 2020: 5 · 2019: 2 · 2018: 2 · 2017: 1
- FWCI
- 0.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Translational research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Department of Biotechnology (DBT), Government of India (BT/PR8597/MED/29/764/2013)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Vectors
- Social Sciences › Sociology and Political Science › Dengue and Mosquito Control Research
- Keywords
- dengue, severe dengue, disease progression, peripheral blood mononuclear cells, gene expression signatures, prognostic factors, neutrophil activation, neutrophil degranulation, myeloperoxidase, neutrophil elastase, cell-free DNA, inflammation, cytokines, glycine, serine and threonine metabolism, extracellular matrix organization, ubiquitination, febrile illness
- MeSH terms
- Adolescent, Adult, Base Sequence, Child, Dengue, Dengue Virus, Female, Gene Expression Regulation, Humans, Leukocytes, Mononuclear, Male, RNA, Transcription, Genetic, Young Adult, Transcriptome
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