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

Publication date: Available online 17 June 2017
Source:Translational Research
Author(s): Arup Banerjee, Shweta Shukla, Abhay Deep Pandey, Saptamita Goswami, Bhaswati Bandyopadhyay, Vishnampettai Ramachandran, Shukla Das, Arjun Malhotra, Amitesh Agarwal, Srima Adhikari, Mehebubar Rahman, Shatakshee Chatterjee, Nemai Bhattacharya, Nandita Basu, Priyanka Pandey, Vikas Sood, Sudhanshu Vrati
Patients infected with Dengue virus usually present a mild, self-limiting febrile dengue illness (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 highthroughput 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 the other febrile illness (OFI) or the healthy controls. The transcriptional signatures that discriminated the DS patients from the OFI and DI patients were broadly related to the pathways involving glycine, serine and threonine metabolism, 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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