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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Public Library of Science
2018
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| Online Access: | http://hdl.handle.net/1721.1/114929 |
| _version_ | 1811006023471726592 |
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| author | Cui, Liang Pang, Junxiong Lee, Yie Hou Ooi, Eng Eong Ong, Choon Nam Leo, Yee Sin Tannenbaum, Steven R |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Cui, Liang Pang, Junxiong Lee, Yie Hou Ooi, Eng Eong Ong, Choon Nam Leo, Yee Sin Tannenbaum, Steven R |
| author_sort | Cui, Liang |
| collection | MIT |
| 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. |
| first_indexed | 2024-09-23T16:45:31Z |
| format | Article |
| id | mit-1721.1/114929 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T16:45:31Z |
| publishDate | 2018 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/1149292022-10-03T08:06:05Z Serum metabolome changes in adult patients with severe dengue in the critical and recovery phases of dengue infection Cui, Liang Pang, Junxiong Lee, Yie Hou Ooi, Eng Eong Ong, Choon Nam Leo, Yee Sin Tannenbaum, Steven R Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Chemistry Tannenbaum, Steven R 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. 2018-04-24T15:10:19Z 2018-04-24T15:10:19Z 2018-01 2017-05 2018-04-20T17:26:42Z Article http://purl.org/eprint/type/JournalArticle 1935-2735 http://hdl.handle.net/1721.1/114929 Cui, Liang et al. “Serum Metabolome Changes in Adult Patients with Severe Dengue in the Critical and Recovery Phases of Dengue Infection.” Edited by Eva Harris. PLOS Neglected Tropical Diseases 12, 1 (January 2018): e0006217 © 2018 Cui et al http://dx.doi.org/10.1371/journal.pntd.0006217 PLOS Neglected Tropical Diseases Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Public Library of Science PLoS |
| spellingShingle | Cui, Liang Pang, Junxiong Lee, Yie Hou Ooi, Eng Eong Ong, Choon Nam Leo, Yee Sin Tannenbaum, Steven R Serum metabolome changes in adult patients with severe dengue in the critical and recovery phases of dengue infection |
| title | 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_short | 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 |
| url | http://hdl.handle.net/1721.1/114929 |
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