Abstract
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.
Highlights
Dengue is a re-emerging disease caused by four closely related serotypes of dengue viruses (DENV) and it is endemic in the tropical and sub-tropical regions of the world
DENV can cause a spectrum of clinical manifestations ranging from mild dengue fever (DF) to the potentially lethal dengue hemorrhagic fever (DHF)
To gain insights on the mechanisms of DHF pathogenesis, we performed metabolomic profiling of sera from adult DF and DHF patients at the critical phase of infection (5–7 days after onset of fever), the time point when the clinical symptoms of DHF become more evident. 29 differentially expressed metabolites between DF and DHF were identified, allowing us to discover a variety of metabolite pathways linked to DHF
Summary
Dengue is a re-emerging disease caused by four closely related serotypes of dengue viruses (DENV) and it is endemic in the tropical and sub-tropical regions of the world. Infection with DENV can cause a spectrum of clinical manifestations ranging from mild dengue fever (DF) to the potentially lethal dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), which are characterized by abnormal hemostasis, vascular leakage and liver damage [2]. There is no specific treatment for dengue and the management of DHF patients is primarily supportive. DF patients would recover uneventfully after 5–7 days of acute illness, but for DHF patients, the initial febrile period is followed by a rapid onset of vascular leakage, thrombocytopenia and hemorrhage at the critical phase. Numerous efforts have been made in the last decade [3,4,5,6], the mechanisms that trigger transition from mild DF to more life threatening DHF at the critical phase are not fully understood, hampering the design of effective treatments for DHF
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
