Serum metabolome changes in adult patients with severe dengue in the critical and recovery phases of dengue infection.
Dengue virus (DENV) is the most prevalent arbovirus leading to an estimated 100 million symptomatic dengue infections every year. DENV can cause a spectrum of clinical manifestations, ranging from mild dengue fever (DF) to more life threatening forms such as dengue hemorrhagic fever (DHF). The clini...
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ftdoajarticles:oai:doaj.org/article:bf2433bcb1a148089af2be04a45bdbd0 2023-05-15T15:15:41+02:00 Serum metabolome changes in adult patients with severe dengue in the critical and recovery phases of dengue infection. Liang Cui Junxiong Pang Yie Hou Lee Eng Eong Ooi Choon Nam Ong Yee Sin Leo Steven R Tannenbaum 2018-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0006217 https://doaj.org/article/bf2433bcb1a148089af2be04a45bdbd0 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5798853?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006217 https://doaj.org/article/bf2433bcb1a148089af2be04a45bdbd0 PLoS Neglected Tropical Diseases, Vol 12, Iss 1, p e0006217 (2018) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2018 ftdoajarticles https://doi.org/10.1371/journal.pntd.0006217 2022-12-31T14:37:03Z Dengue virus (DENV) is the most prevalent arbovirus leading to an estimated 100 million symptomatic dengue infections every year. DENV can cause a spectrum of clinical manifestations, ranging from mild dengue fever (DF) to more life threatening forms such as dengue hemorrhagic fever (DHF). The clinical symptoms of DHF become evident typically at the critical phase of infection (5-7 days after onset of fever), yet the mechanisms that trigger transition from DF to DHF are not well understood. We performed a mass spectrometry-based metabolomic profiling of sera from adult DF and DHF patients at the critical and recovery phases of infection. There were 29 differentially expressed metabolites identified between DF and DHF at the critical phase. These include bile acids, purines, acylcarnitines, phospholipids, and amino acids. Bile acids were observed up to 5 fold higher levels among DHF compared to DF patients and were significantly correlated to the higher levels of aspartate transaminase (AST) and alanine transaminase (ALT), suggestive of liver injury among DHF. Uric acid, the most abundant antioxidant in the blood, was observed to be 1.5 fold lower among DHF compared to DF patients. This could result in decreased capacity of endogenous antioxidant defense and elevated oxidative stress among DHF patients. In the recovery phase, the levels of eight metabolites were still significantly higher or lower among DHF patients, including chenodeoxyglycocholic acid, one of the bile acids observed at the critical phase. This indicates potential prolonged adverse impact on the liver due to DENV infection in DHF patients. Our study identified altered metabolic pathways linked to DHF in the critical and recovery phases of dengue infection and provided insights into the different host and DENV interactions between DF and DHF. The results advance our understanding on the mechanisms of DHF pathogenesis, alluding to possible novel therapeutic targets to dengue management. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 12 1 e0006217 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Liang Cui Junxiong Pang Yie Hou Lee Eng Eong Ooi Choon Nam Ong Yee Sin Leo Steven R Tannenbaum Serum metabolome changes in adult patients with severe dengue in the critical and recovery phases of dengue infection. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Dengue virus (DENV) is the most prevalent arbovirus leading to an estimated 100 million symptomatic dengue infections every year. DENV can cause a spectrum of clinical manifestations, ranging from mild dengue fever (DF) to more life threatening forms such as dengue hemorrhagic fever (DHF). The clinical symptoms of DHF become evident typically at the critical phase of infection (5-7 days after onset of fever), yet the mechanisms that trigger transition from DF to DHF are not well understood. We performed a mass spectrometry-based metabolomic profiling of sera from adult DF and DHF patients at the critical and recovery phases of infection. There were 29 differentially expressed metabolites identified between DF and DHF at the critical phase. These include bile acids, purines, acylcarnitines, phospholipids, and amino acids. Bile acids were observed up to 5 fold higher levels among DHF compared to DF patients and were significantly correlated to the higher levels of aspartate transaminase (AST) and alanine transaminase (ALT), suggestive of liver injury among DHF. Uric acid, the most abundant antioxidant in the blood, was observed to be 1.5 fold lower among DHF compared to DF patients. This could result in decreased capacity of endogenous antioxidant defense and elevated oxidative stress among DHF patients. In the recovery phase, the levels of eight metabolites were still significantly higher or lower among DHF patients, including chenodeoxyglycocholic acid, one of the bile acids observed at the critical phase. This indicates potential prolonged adverse impact on the liver due to DENV infection in DHF patients. Our study identified altered metabolic pathways linked to DHF in the critical and recovery phases of dengue infection and provided insights into the different host and DENV interactions between DF and DHF. The results advance our understanding on the mechanisms of DHF pathogenesis, alluding to possible novel therapeutic targets to dengue management. |
format |
Article in Journal/Newspaper |
author |
Liang Cui Junxiong Pang Yie Hou Lee Eng Eong Ooi Choon Nam Ong Yee Sin Leo Steven R Tannenbaum |
author_facet |
Liang Cui Junxiong Pang Yie Hou Lee Eng Eong Ooi Choon Nam Ong Yee Sin Leo Steven R Tannenbaum |
author_sort |
Liang Cui |
title |
Serum metabolome changes in adult patients with severe dengue in the critical and recovery phases of dengue infection. |
title_short |
Serum metabolome changes in adult patients with severe dengue in the critical and recovery phases of dengue infection. |
title_full |
Serum metabolome changes in adult patients with severe dengue in the critical and recovery phases of dengue infection. |
title_fullStr |
Serum metabolome changes in adult patients with severe dengue in the critical and recovery phases of dengue infection. |
title_full_unstemmed |
Serum metabolome changes in adult patients with severe dengue in the critical and recovery phases of dengue infection. |
title_sort |
serum metabolome changes in adult patients with severe dengue in the critical and recovery phases of dengue infection. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2018 |
url |
https://doi.org/10.1371/journal.pntd.0006217 https://doaj.org/article/bf2433bcb1a148089af2be04a45bdbd0 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 12, Iss 1, p e0006217 (2018) |
op_relation |
http://europepmc.org/articles/PMC5798853?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006217 https://doaj.org/article/bf2433bcb1a148089af2be04a45bdbd0 |
op_doi |
https://doi.org/10.1371/journal.pntd.0006217 |
container_title |
PLOS Neglected Tropical Diseases |
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12 |
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1 |
container_start_page |
e0006217 |
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1766346032318251008 |