10.1371/journal.pntd.0002373PLoS Neglected Tropical Diseases78

A Mangerich

A Mathew

A Sreekumar

A Zuniga

AL St John

B Brugger

BR Murphy

C Lu

C Rothwell

CF Nathan

Choon Nam Ong

CN Serhan

DJ Gubler

DL Diamond

DP Ng

E Avota

E Sandalova

E Zaitseva

E Zigmond

EC Laiakis

EG Bligh

EL Azeredo

Eng Eong Ooi

F Facciotti

Fengguo Xu

G Birungi

G Hasko

GF Nixon

J Chen

J Guarner

J Herz

J Mattner

J Xia

JC Suvarna

JG Low

JH Yang

JK Nicholson

K Izawa

K Jessie

K Myo

Kun Lu

L Gil

Liang Cui

MC Ruzek

ME Miller

MG Guzman

N Vinayavekhin

NS Heaton

P Klassen

PC Calder

PC Neves-Souza

PG Hellewell

PJ Brennan

R Al-Mubarak

R Takhampunya

RA Lewis

RC Seet

RL Shaner

RW Wannemacher Jr

S Noisakran

SB Halstead

Scott F. Michael

SJ Gagnon

SL Tilley

Steven R. Tannenbaum

T Akaike

T Kawano

T Pluskal

TJ Nevalainen

W Shi

WW Goh

X Han

Y Kumar

YA Hannun

Yadunanda Kumar

Yie Hou Lee

Z Wang

PLoS Neglected Tropical Diseases

PubMed

<div>BackgroundDengue virus (DENV) is the most widespread arbovirus with an estimated 100 million infections occurring every year. Endemic in the tropical and subtropical areas of the world, dengue fever/dengue hemorrhagic fever (DF/DHF) is emerging as a major public health concern. The complex array of concurrent host physiologic changes has hampered a complete understanding of underlying molecular mechanisms of dengue pathogenesis.Methodology/Principle FindingsSystems level characterization of serum metabolome and lipidome of adult DF patients at early febrile, defervescence, and convalescent stages of DENV infection was performed using liquid chromatography- and gas chromatography-mass spectrometry. The tractability of following metabolite and lipid changes in a relatively large sample size (n = 44) across three prominent infection stages allowed the identification of critical physiologic changes that coincided with the different stages. Sixty differential metabolites were identified in our metabolomics analysis and the main metabolite classes were free fatty acids, acylcarnitines, phospholipids, and amino acids. Major perturbed metabolic pathways included fatty acid biosynthesis and β-oxidation, phospholipid catabolism, steroid hormone pathway, etc., suggesting the multifactorial nature of human host responses. Analysis of phospholipids and sphingolipids verified the temporal trends and revealed association with lymphocytes and platelets numbers. These metabolites were significantly perturbed during the early stages, and normalized to control levels at convalescent stage, suggesting their potential utility as prognostic markers.Conclusions/SignificanceDENV infection causes temporally distinct serum metabolome and lipidome changes, and many of the differential metabolites are involved in acute inflammatory responses. Our global analyses revealed early anti-inflammatory responses working in concert to modulate early pro-inflammatory processes, thus preventing the host from development of pathologies by excessive or prolonged inflammation. This study is the first example of how an omic- approach can divulge the extensive, concurrent, and dynamic host responses elicited by DENV and offers plausible physiological insights to why DF is self limiting.</div

Liang Cui (446525)

Yie Hou Lee (327357)

Yadunanda Kumar (116473)

Fengguo Xu (446526)

Kun Lu (404977)

Eng Eong Ooi (56879)

Steven R. Tannenbaum (116488)

Choon Nam Ong (192183)

The Francis Crick Institute

Serum Metabolome and Lipidome Changes in Adult Patients with Primary Dengue Infection

Dengue virus (DENV) is the most widespread arbovirus with an estimated 100 million infections occurring every year. Endemic in the tropical and subtropical areas of the world, dengue fever/dengue hemorrhagic fever (DF/DHF) is emerging as a major public health concern. The complex array of concurrent host physiologic changes has hampered a complete understanding of underlying molecular mechanisms of dengue pathogenesis.-oxidation, phospholipid catabolism, steroid hormone pathway, etc., suggesting the multifactorial nature of human host responses. Analysis of phospholipids and sphingolipids verified the temporal trends and revealed association with lymphocytes and platelets numbers. These metabolites were significantly perturbed during the early stages, and normalized to control levels at convalescent stage, suggesting their potential utility as prognostic markers.DENV infection causes temporally distinct serum metabolome and lipidome changes, and many of the differential metabolites are involved in acute inflammatory responses. Our global analyses revealed early anti-inflammatory responses working in concert to modulate early pro-inflammatory processes, thus preventing the host from development of pathologies by excessive or prolonged inflammation. This study is the first example of how an omic- approach can divulge the extensive, concurrent, and dynamic host responses elicited by DENV and offers plausible physiological insights to why DF is self limiting

Cui Liang

Lee Yie Hou

Kumar Yadunanda

Xu Fengguo

Lu Kun

Ooi Eng Eong

Tannenbaum Steven R.

Ong Choon Nam

Public Library of Science (PLOS)

Crossref

Background:
Dengue virus (DENV) is the most widespread arbovirus with an estimated 100 million infections occurring every year. Endemic in the tropical and subtropical areas of the world, dengue fever/dengue hemorrhagic fever (DF/DHF) is emerging as a major public health concern. The complex array of concurrent host physiologic changes has hampered a complete understanding of underlying molecular mechanisms of dengue pathogenesis.
Methodology/Principle Findings:
Systems level characterization of serum metabolome and lipidome of adult DF patients at early febrile, defervescence, and convalescent stages of DENV infection was performed using liquid chromatography- and gas chromatography-mass spectrometry. The tractability of following metabolite and lipid changes in a relatively large sample size (n = 44) across three prominent infection stages allowed the identification of critical physiologic changes that coincided with the different stages. Sixty differential metabolites were identified in our metabolomics analysis and the main metabolite classes were free fatty acids, acylcarnitines, phospholipids, and amino acids. Major perturbed metabolic pathways included fatty acid biosynthesis and β-oxidation, phospholipid catabolism, steroid hormone pathway, etc., suggesting the multifactorial nature of human host responses. Analysis of phospholipids and sphingolipids verified the temporal trends and revealed association with lymphocytes and platelets numbers. These metabolites were significantly perturbed during the early stages, and normalized to control levels at convalescent stage, suggesting their potential utility as prognostic markers.
Conclusions/Significance:
DENV infection causes temporally distinct serum metabolome and lipidome changes, and many of the differential metabolites are involved in acute inflammatory responses. Our global analyses revealed early anti-inflammatory responses working in concert to modulate early pro-inflammatory processes, thus preventing the host from development of pathologies by excessive or prolonged inflammation. This study is the first example of how an omic- approach can divulge the extensive, concurrent, and dynamic host responses elicited by DENV and offers plausible physiological insights to why DF is self limiting.Singapore-MIT Alliance for Research and Technolog

Cui, Liang

Lee, Yie Hou

Kumar, Yadunanda

Xu, Fengguo

Lu, Kun

Ooi, Eng Eong

Ong, Choon Nam

Tannenbaum, Steven Robert

DSpace@MIT

Dengue virus (DENV) is the most widespread arbovirus with an estimated 100 million infections occurring every year. Endemic in the tropical and subtropical areas of the world, dengue fever/dengue hemorrhagic fever (DF/DHF) is emerging as a major public health concern. The complex array of concurrent host physiologic changes has hampered a complete understanding of underlying molecular mechanisms of dengue pathogenesis.Systems level characterization of serum metabolome and lipidome of adult DF patients at early febrile, defervescence, and convalescent stages of DENV infection was performed using liquid chromatography- and gas chromatography-mass spectrometry. The tractability of following metabolite and lipid changes in a relatively large sample size (n = 44) across three prominent infection stages allowed the identification of critical physiologic changes that coincided with the different stages. Sixty differential metabolites were identified in our metabolomics analysis and the main metabolite classes were free fatty acids, acylcarnitines, phospholipids, and amino acids. Major perturbed metabolic pathways included fatty acid biosynthesis and β-oxidation, phospholipid catabolism, steroid hormone pathway, etc., suggesting the multifactorial nature of human host responses. Analysis of phospholipids and sphingolipids verified the temporal trends and revealed association with lymphocytes and platelets numbers. These metabolites were significantly perturbed during the early stages, and normalized to control levels at convalescent stage, suggesting their potential utility as prognostic markers.DENV infection causes temporally distinct serum metabolome and lipidome changes, and many of the differential metabolites are involved in acute inflammatory responses. Our global analyses revealed early anti-inflammatory responses working in concert to modulate early pro-inflammatory processes, thus preventing the host from development of pathologies by excessive or prolonged inflammation. This study is the first example of how an omic- approach can divulge the extensive, concurrent, and dynamic host responses elicited by DENV and offers plausible physiological insights to why DF is self limiting

Steven R Tannenbaum

Directory of Open Access Journals

Serum metabolome and lipidome changes in adult patients with primary dengue infection.

Serum Metabolome and Lipidome Changes in Adult Patients with Primary Dengue Infection

Abstract

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The Francis Crick Institute

Public Library of Science (PLOS)

Crossref

DSpace@MIT

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Directory of Open Access Journals