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Transl Res. 2017 Aug;186:62-78.e9. doi: 10.1016/j.trsl.2017.06.007. Epub 2017 Jun 17.

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

Author information

1
Vaccine and Infectious Disease Research Center (VIDRC), Translational Health Science and Technology Institute (THSTI), Faridabad, Haryana, India. Electronic address: banerjeea@thsti.res.in.
2
University College of Medical Sciences (UCMS) & Guru Teg Bahadur (GTB) Hospital, Delhi, Delhi, India.
3
Vaccine and Infectious Disease Research Center (VIDRC), Translational Health Science and Technology Institute (THSTI), Faridabad, Haryana, India.
4
Virology Unit, Department of Microbiology, Calcutta School of Tropical Medicine (STM), Kolkata, West Bengal, India.
5
National Institute of Biomedical Genomics (NIBMG), Kalyani, West Bengal, India.
6
Vaccine and Infectious Disease Research Center (VIDRC), Translational Health Science and Technology Institute (THSTI), Faridabad, Haryana, India; Regional Center for Biotechnology (RCB), Faridabad, Haryana, India. Electronic address: vrati@rcb.res.in.

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.

PMID:
28683259
DOI:
10.1016/j.trsl.2017.06.007
[Indexed for MEDLINE]

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