Dual RNA-Seq reveals transcriptionally active microbes (TAMs) dynamics in the serum of dengue patients associated with disease severity

IntroductionDengue virus (DENV) is a flavivirus that has emerged as a global health threat, characterized by either asymptomatic or mild self-limiting febrile illness, but a subset of DENV outbreaks have been associated with severe disease. Studies have looked into the host immune response and dengu...

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Main Authors: Aanchal Yadav, Pallawi Kumari, Priti Devi, Jorelle Jeanne B. Adjele, Sandeep Budhiraja, Bansidhar Tarai, Rajesh Pandey
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-11-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2023.1307859/full
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author Aanchal Yadav
Aanchal Yadav
Pallawi Kumari
Pallawi Kumari
Priti Devi
Priti Devi
Jorelle Jeanne B. Adjele
Jorelle Jeanne B. Adjele
Sandeep Budhiraja
Bansidhar Tarai
Rajesh Pandey
Rajesh Pandey
author_facet Aanchal Yadav
Aanchal Yadav
Pallawi Kumari
Pallawi Kumari
Priti Devi
Priti Devi
Jorelle Jeanne B. Adjele
Jorelle Jeanne B. Adjele
Sandeep Budhiraja
Bansidhar Tarai
Rajesh Pandey
Rajesh Pandey
author_sort Aanchal Yadav
collection DOAJ
description IntroductionDengue virus (DENV) is a flavivirus that has emerged as a global health threat, characterized by either asymptomatic or mild self-limiting febrile illness, but a subset of DENV outbreaks have been associated with severe disease. Studies have looked into the host immune response and dengue viral load during infection. However, it remains unknown how the active microbial isolates modulate the dengue viral infection. In this study, we demonstrate the significance of in-depth analysis of microbiota composition in the serum samples of dengue-infected patients.Materials and methodsRNA was extracted from the serum samples collected from 24 dengue positive patients. The human mapped reads generated through RNA-Sequencing (RNA-Seq) were removed, while the unmapped (non-human) reads were employed for microbial taxonomic classification using Kraken2 and Bracken2. Further, we assessed the initial blood parameters analyzing the complete blood count (CBC) profile of the patients.ResultsFindings revealed differential abundance of commensals and pathogenic microbes in the early febrile period of hospitalized dengue patients, segregated into, High Viral Reads (HVR) and Low Viral Reads (LVR). The Campylobacter genus was abundant in the HVR whereas Lactobacillus dominated the LVR patients. At species level, the microbiota of HVR exhibited higher abundance of unique potential opportunistic microbes, compared to the commensal microbes’ enrichment in the LVR patients’. We hypothesize that the DENV might alter the microbiota composition as observed by the increase in preponderance of opportunistic pathogens and an absence of commensals in the HVR. The presence of commensals in the LVR might explain, i) overall lower dengue viral reads compared to the HVR, and ii) shift in lymphocytes (high) and neutrophils (low) counts; resulting in a comparatively milder clinical manifestation in this group. Our findings may help in understanding the co-infection aspect that will be important to develop dengue therapeutics and vaccines.DiscussionThis study highlights the potential of the unexplored roles of the TAMs in modulating the dengue disease severity using the metatranscriptomic sequencing. This study serves to enhance our understanding of the distinctive microbial and hematologic signatures in the early infection stage that differentiate patients with high viral reads patients from those with low dengue viral reads.
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spelling doaj.art-c29236dd35124b4c92bbe5000b29746e2023-11-30T07:08:24ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-11-011410.3389/fmicb.2023.13078591307859Dual RNA-Seq reveals transcriptionally active microbes (TAMs) dynamics in the serum of dengue patients associated with disease severityAanchal Yadav0Aanchal Yadav1Pallawi Kumari2Pallawi Kumari3Priti Devi4Priti Devi5Jorelle Jeanne B. Adjele6Jorelle Jeanne B. Adjele7Sandeep Budhiraja8Bansidhar Tarai9Rajesh Pandey10Rajesh Pandey11Division of Immunology and Infectious Disease Biology, INtegrative GENomics of HOst-PathogEn (INGEN-HOPE) Laboratory, CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi, IndiaAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad, IndiaDivision of Immunology and Infectious Disease Biology, INtegrative GENomics of HOst-PathogEn (INGEN-HOPE) Laboratory, CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi, IndiaIndraprastha Institute of Information Technology Delhi, New Delhi, IndiaDivision of Immunology and Infectious Disease Biology, INtegrative GENomics of HOst-PathogEn (INGEN-HOPE) Laboratory, CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi, IndiaAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad, IndiaDivision of Immunology and Infectious Disease Biology, INtegrative GENomics of HOst-PathogEn (INGEN-HOPE) Laboratory, CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi, IndiaCentre for Food, Food Security, and Nutrition Research, Institute of Medical Research and Medicinal Plant Studies, Yaounde, CameroonMax Super Speciality Hospital (A Unit of Devki Devi Foundation), Max Healthcare, Delhi, IndiaMax Super Speciality Hospital (A Unit of Devki Devi Foundation), Max Healthcare, Delhi, IndiaDivision of Immunology and Infectious Disease Biology, INtegrative GENomics of HOst-PathogEn (INGEN-HOPE) Laboratory, CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi, IndiaAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad, IndiaIntroductionDengue virus (DENV) is a flavivirus that has emerged as a global health threat, characterized by either asymptomatic or mild self-limiting febrile illness, but a subset of DENV outbreaks have been associated with severe disease. Studies have looked into the host immune response and dengue viral load during infection. However, it remains unknown how the active microbial isolates modulate the dengue viral infection. In this study, we demonstrate the significance of in-depth analysis of microbiota composition in the serum samples of dengue-infected patients.Materials and methodsRNA was extracted from the serum samples collected from 24 dengue positive patients. The human mapped reads generated through RNA-Sequencing (RNA-Seq) were removed, while the unmapped (non-human) reads were employed for microbial taxonomic classification using Kraken2 and Bracken2. Further, we assessed the initial blood parameters analyzing the complete blood count (CBC) profile of the patients.ResultsFindings revealed differential abundance of commensals and pathogenic microbes in the early febrile period of hospitalized dengue patients, segregated into, High Viral Reads (HVR) and Low Viral Reads (LVR). The Campylobacter genus was abundant in the HVR whereas Lactobacillus dominated the LVR patients. At species level, the microbiota of HVR exhibited higher abundance of unique potential opportunistic microbes, compared to the commensal microbes’ enrichment in the LVR patients’. We hypothesize that the DENV might alter the microbiota composition as observed by the increase in preponderance of opportunistic pathogens and an absence of commensals in the HVR. The presence of commensals in the LVR might explain, i) overall lower dengue viral reads compared to the HVR, and ii) shift in lymphocytes (high) and neutrophils (low) counts; resulting in a comparatively milder clinical manifestation in this group. Our findings may help in understanding the co-infection aspect that will be important to develop dengue therapeutics and vaccines.DiscussionThis study highlights the potential of the unexplored roles of the TAMs in modulating the dengue disease severity using the metatranscriptomic sequencing. This study serves to enhance our understanding of the distinctive microbial and hematologic signatures in the early infection stage that differentiate patients with high viral reads patients from those with low dengue viral reads.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1307859/fulldengue infectionhigh and low dengue viral readsclinical parametersdual RNA-Seqtranscriptionally active microbesdisease severity
spellingShingle Aanchal Yadav
Aanchal Yadav
Pallawi Kumari
Pallawi Kumari
Priti Devi
Priti Devi
Jorelle Jeanne B. Adjele
Jorelle Jeanne B. Adjele
Sandeep Budhiraja
Bansidhar Tarai
Rajesh Pandey
Rajesh Pandey
Dual RNA-Seq reveals transcriptionally active microbes (TAMs) dynamics in the serum of dengue patients associated with disease severity
Frontiers in Microbiology
dengue infection
high and low dengue viral reads
clinical parameters
dual RNA-Seq
transcriptionally active microbes
disease severity
title Dual RNA-Seq reveals transcriptionally active microbes (TAMs) dynamics in the serum of dengue patients associated with disease severity
title_full Dual RNA-Seq reveals transcriptionally active microbes (TAMs) dynamics in the serum of dengue patients associated with disease severity
title_fullStr Dual RNA-Seq reveals transcriptionally active microbes (TAMs) dynamics in the serum of dengue patients associated with disease severity
title_full_unstemmed Dual RNA-Seq reveals transcriptionally active microbes (TAMs) dynamics in the serum of dengue patients associated with disease severity
title_short Dual RNA-Seq reveals transcriptionally active microbes (TAMs) dynamics in the serum of dengue patients associated with disease severity
title_sort dual rna seq reveals transcriptionally active microbes tams dynamics in the serum of dengue patients associated with disease severity
topic dengue infection
high and low dengue viral reads
clinical parameters
dual RNA-Seq
transcriptionally active microbes
disease severity
url https://www.frontiersin.org/articles/10.3389/fmicb.2023.1307859/full
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