scholarly journals Melatonin Inhibits Dengue Virus Infection via the Sirtuin 1-Mediated Interferon Pathway

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 659
Author(s):  
Atthapan Morchang ◽  
Shilu Malakar ◽  
Kanchanaphan Poonudom ◽  
Sansanee Noisakran ◽  
Pa-thai Yenchitsomanus ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Production Cross ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Cell Types ◽  
Denv Infection ◽  
Sirtuin 1 ◽  
Natural Hormone ◽  
New Strategy ◽  
Post Entry

Dengue virus (DENV) is the causative pathogen in the life-threatening dengue hemorrhagic fever and dengue shock syndrome. DENV is transmitted to humans via the bite of an infected Aedes mosquito. Approximately 100 million people are infected annually worldwide, and most of those live in tropical and subtropical areas. There is still no effective drug or vaccine for treatment of DENV infection. In this study, we set forth to investigate the effect of melatonin, which is a natural hormone with multiple pharmacological functions, against DENV infection. Treatment with subtoxic doses of melatonin dose-dependently inhibited DENV production. Cross-protection across serotypes and various cell types was also observed. Time-of-addition assay suggested that melatonin exerts its influence during the post-entry step of viral infection. The antiviral activity of melatonin partly originates from activation of the sirtuin pathway since co-treatment with melatonin and the sirtuin 1 (SIRT1) inhibitor reversed the effect of melatonin treatment alone. Moreover, melatonin could modulate the transcription of antiviral genes that aid in suppression of DENV production. This antiviral mechanism of melatonin suggests a possible new strategy for treating DENV infection.

scholarly journals Pathogenic Roles of Macrophage Migration Inhibitory Factor during Dengue Virus Infection

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Yung-Chun Chuang ◽  
Hong-Ru Chen ◽  
Trai-Ming Yeh
Keyword(s):  
Dengue Virus ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Immune Cell ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Denv Infection ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Knock Out

Dengue virus (DENV) infection is the most common cause of viral hemorrhagic fever, which can lead to life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Hemorrhage and plasma leakage are two major hallmarks of DHF/DSS. Because the mechanisms causing these pathogenic changes are unclear, there is no effective therapy against DHF/DSS. In this review, we focus on the possible pathogenic effects of a pleiotropic cytokine, macrophage migration inhibitory factor (MIF), on the pathogenesis of DENV infection. MIF is a critical mediator of the host immune response and inflammation, and there is a correlation between the serum levels of MIF and disease severity in dengue patients. Furthermore, MIF knock-out mice exhibit less severe clinical disease and lethality. However, the role of MIF in the pathogenesis of DHF/DSS is not limited to immune cell recruitment. Recent evidence indicates that DENV infection induced MIF production and may contribute to vascular hyperpermeability and viral replication during DENV infection. The expression of both adhesion and coagulation molecules on MIF-stimulated monocytes and endothelial cells is also increased, which may contribute to inflammatory and anticoagulatory states during DHF/DSS. Therefore, blocking MIF production or its function may provide a solution for the treatment and prevention of DHF/DSS.

scholarly journals A Novel Role for the Regulatory Nod-Like Receptor NLRP12 in Anti-Dengue Virus Response

2021 ◽  
Vol 12 ◽  
Author(s):  
Xingyu Li ◽  
Zhuo Dong ◽  
Yan Liu ◽  
Weifeng Song ◽  
Jieying Pu ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Denv Infection ◽  
Poly I:C ◽  
Severe Illness ◽  
Human Macrophage ◽  
Type I ◽  
Zikv Infection ◽  
Type I Ifns

Dengue Virus (DENV) infection can cause severe illness such as highly fatality dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Innate immune activation by Nod-like receptors (NLRs) is a critical part of host defense against viral infection. Here, we revealed a key mechanism of NLRP12-mediated regulation in DENV infection. Firstly, NLRP12 expression was inhibited in human macrophage following DENV or other flaviviruses (JEV, YFV, ZIKV) infection. Positive regulatory domain 1 (PRDM1) was induced by DENV or poly(I:C) and suppressed NLRP12 expression, which was dependent on TBK-1/IRF3 and NF-κB signaling pathways. Moreover, NLRP12 inhibited DENV and other flaviviruses (JEV, YFV, ZIKV) replication, which relied on the well-conserved nucleotide binding structures of its NACHT domain. Furthermore, NLRP12 could interact with heat shock protein 90 (HSP90) dependent on its Walker A and Walker B sites. In addition, NLRP12 enhanced the production of type I IFNs (IFN-α/β) and interferon-stimulated genes (ISGs), including IFITM3, TRAIL and Viperin. Inhibition of HSP90 with 17-DMAG impaired the upregulation of type I IFNs and ISGs induced by NLRP12. Taken together, we demonstrated a novel mechanism that NLRP12 exerted anti-viral properties in DENV and other flaviviruses (JEV, YFV, ZIKV) infection, which brings up a potential target for the treatment of DENV infection.

scholarly journals The Battle between Infection and Host Immune Responses of Dengue Virus and Its Implication in Dengue Disease Pathogenesis

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Peifang Sun ◽  
Tadeusz J. Kochel
Keyword(s):  
Dengue Virus ◽  
Adaptive Immunity ◽  
Inflammatory Responses ◽  
Rna Virus ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Cell Types ◽  
Long Term Memory ◽  
Dengue Disease ◽  
Host Immune Responses

Dengue virus (DENV) is a mosquito-transmitted single stranded RNA virus belonging to genusFlavivirus. The virus is endemic in the tropical and subtropical countries of the world, causing diseases classified according to symptoms and severity (from mild to severe) as dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Among a variety of human cell types targeted by DENV, monocytes, macrophages, and dendritic cells are members of innate immunity, capable of mounting rapid inflammatory responses. These cells are also major antigen presenting cells, responsible for activating the adaptive immunity for long-term memory. This paper is an overview of the current understanding of the following mutually affected aspects: DENV structure, viral infectivity, cellular receptors, innate immune response, and adaptive immunity.

scholarly journals UPDATE MANAGEMENT OF DENGUE COMPLICATION IN PEDIATRIC

2015 ◽  
Vol 2 (1) ◽  
pp. 1
Author(s):  
Soegeng Soegijanto
Keyword(s):  
Virus Infection ◽  
Dengue Virus ◽  
Clinical Performance ◽  
Kidney Injury ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Liver Involvement ◽  
Dengue Virus Infection ◽  
Important Health ◽  
Grade Iii

Dengue virus infection is one of the important health problems in Indonesia, although the mortality rate has been decreased but many dengue shock syndrome cases is very difficult to be solving handled. It might be due to nature course of dengue virus infection is very difficult to predict of the earlier time of severity occur. THE AIM To get idea to make update management of dengue complication in pediatric. MATERIAL AND METHOD Data were compiled from Dr. Soetomo Hospital Surabaya in 2009. The diagnosis of all cases was based on criteria WHO 1997 and PCR examination in Institute Tropical Disease for identified serotype of dengue virus infection. The unusual cases of dengue virus infection were treated following the new WHO protocol in 2009. RESULT There were only 3 cases with serotype DEN 1, consisted 2 cases had age 1–4 years and 1 had age 5–14 years. 2 cases showed a severe clinical performance as dengue shock syndrome and 1 case showed as unusual case of dengue virus infection. Three report cases of: a. Dengue hemorrhagic fever grade III which liver involvement and had bilateral pleural effusion; b. Dengue hemorrhagic grade III with liver involvement and encephalopathy; c. Dengue hemorrhagic grade III with liver involvement acute kidney injury, myocardial involvement and encephalopathy. All the patients were treated according to new edition WHO protocol and all of the involving organ recovered along with the improvement of the disease. CONCLUSION Update management of dengue complication pediatric should be learned carefully used for helping unusual cases of dengue virus infection.

scholarly journals Dengue Virus Targets Nrf2 for NS2B3-Mediated Degradation Leading to Enhanced Oxidative Stress and Viral Replication

2020 ◽  
Vol 94 (24) ◽  
Author(s):  
Matteo Ferrari ◽  
Alessandra Zevini ◽  
Enrico Palermo ◽  
Michela Muscolini ◽  
Magdalini Alexandridi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Dengue Virus ◽  
Redox Homeostasis ◽  
Reactive Oxygen ◽  
Hemorrhagic Fever ◽  
Denv Infection ◽  
Progressive Increase ◽  
Severe Dengue ◽  
Oxygen Species

ABSTRACT Dengue virus (DENV) is a mosquito-borne virus that infects upward of 300 million people annually and has the potential to cause fatal hemorrhagic fever and shock. While the parameters contributing to dengue immunopathogenesis remain unclear, the collapse of redox homeostasis and the damage induced by oxidative stress have been correlated with the development of inflammation and progression toward the more severe forms of disease. In the present study, we demonstrate that the accumulation of reactive oxygen species (ROS) late after DENV infection (>24 hpi) resulted from a disruption in the balance between oxidative stress and the nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent antioxidant response. The DENV NS2B3 protease complex strategically targeted Nrf2 for degradation in a proteolysis-independent manner; NS2B3 licensed Nrf2 for lysosomal degradation. Impairment of the Nrf2 regulator by the NS2B3 complex inhibited the antioxidant gene network and contributed to the progressive increase in ROS levels, along with increased virus replication and inflammatory or apoptotic gene expression. By 24 hpi, when increased levels of ROS and antiviral proteins were observed, it appeared that the proviral effect of ROS overcame the antiviral effects of the interferon (IFN) response. Overall, these studies demonstrate that DENV infection disrupts the regulatory interplay between DENV-induced stress responses, Nrf2 antioxidant signaling, and the host antiviral immune response, thus exacerbating oxidative stress and inflammation in DENV infection. IMPORTANCE Dengue virus (DENV) is a mosquito-borne pathogen that threatens 2.5 billion people in more than 100 countries annually. Dengue infection induces a spectrum of clinical symptoms, ranging from classical dengue fever to severe dengue hemorrhagic fever or dengue shock syndrome; however, the complexities of DENV immunopathogenesis remain controversial. Previous studies have reported the importance of the transcription factor Nrf2 in the control of redox homeostasis and antiviral/inflammatory or death responses to DENV. Importantly, the production of reactive oxygen species and the subsequent stress response have been linked to the development of inflammation and progression toward the more severe forms of the disease. Here, we demonstrate that DENV uses the NS2B3 protease complex to strategically target Nrf2 for degradation, leading to a progressive increase in oxidative stress, inflammation, and cell death in infected cells. This study underlines the pivotal role of the Nrf2 regulatory network in the context of DENV infection.

scholarly journals Roles for Endothelial Cells in Dengue Virus Infection

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Nadine A. Dalrymple ◽  
Erich R. Mackow
Keyword(s):  
Virus Infection ◽  
Dengue Virus ◽  
Capillary Permeability ◽  
Virus Disease ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Dengue Virus Infection ◽  
Barrier Functions ◽  
Dengue Disease ◽  
Primary Fluid

Dengue viruses cause two severe diseases that alter vascular fluid barrier functions, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The endothelium is the primary fluid barrier of the vasculature and ultimately the effects of dengue virus infection that cause capillary leakage impact endothelial cell (EC) barrier functions. The ability of dengue virus to infect the endothelium provides a direct means for dengue to alter capillary permeability, permit virus replication, and induce responses that recruit immune cells to the endothelium. Recent studies focused on dengue virus infection of primary ECs have demonstrated that ECs are efficiently infected, rapidly produce viral progeny, and elicit immune enhancing cytokine responses that may contribute to pathogenesis. Furthermore, infected ECs have also been implicated in enhancing viremia and immunopathogenesis within murine dengue disease models. Thus dengue-infected ECs have the potential to directly contribute to immune enhancement, capillary permeability, viremia, and immune targeting of the endothelium. These effects implicate responses of the infected endothelium in dengue pathogenesis and rationalize therapeutic targeting of the endothelium and EC responses as a means of reducing the severity of dengue virus disease.

scholarly journals Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Ashley L St John ◽  
Abhay PS Rathore ◽  
Bhuvanakantham Raghavan ◽  
Mah-Lee Ng ◽  
Soman N Abraham
Keyword(s):  
Mast Cells ◽  
Dengue Virus ◽  
Hemorrhagic Fever ◽  
Denv Infection ◽  
Vascular Leakage ◽  
Clinical Samples ◽  
Specific Product ◽  
Hemorrhagic Fevers ◽  
Viral Hemorrhagic Fevers

Dengue Virus (DENV), a flavivirus spread by mosquito vectors, can cause vascular leakage and hemorrhaging. However, the processes that underlie increased vascular permeability and pathological plasma leakage during viral hemorrhagic fevers are largely unknown. Mast cells (MCs) are activated in vivo during DENV infection, and we show that this elevates systemic levels of their vasoactive products, including chymase, and promotes vascular leakage. Treatment of infected animals with MC-stabilizing drugs or a leukotriene receptor antagonist restores vascular integrity during experimental DENV infection. Validation of these findings using human clinical samples revealed a direct correlation between MC activation and DENV disease severity. In humans, the MC-specific product, chymase, is a predictive biomarker distinguishing dengue fever (DF) and dengue hemorrhagic fever (DHF). Additionally, our findings reveal MCs as potential therapeutic targets to prevent DENV-induced vasculopathy, suggesting MC-stabilizing drugs should be evaluated for their effectiveness in improving disease outcomes during viral hemorrhagic fevers.

scholarly journals Serotype Infectivity and Phylogenetic of Dengue Virus cause of Dengue Fever (DF), Dengue Hemorrhagic Fever (DHF), and Dengue Shock Syndrome (DSS) in Surabaya- Indonesia

2020 ◽  
Vol 4 (1) ◽  
pp. 1
Author(s):  
Fedik Rantam
Keyword(s):  
Phylogenetic Analysis ◽  
Nucleotide Sequence ◽  
Dengue Virus ◽  
Dengue Infection ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Rt Pcr ◽  
Who Criteria ◽  
Plasma Leakage ◽  
Degree Of Severity

Infection with DENV causes a spectrum of clinical disease ranging. The aim of this study is to investigate the infectivity of DENV with degree of severity dengue infection in Surabaya. Dengue infection was established by IgM anti dengue, and two step multiplex RT PCR and Nucleotide sequence. Grading of degree severity infection follow the WHO criteria 2011. DSS cases found 3 from 36 patients caused by DENV 2. The most uninfective was DENV 1, and the most prevalence dengue infection caused  by  DENV  3.  The  infectivity of  dengue  infection shown 16 patients lead to severity with plasma leakage. All of sera patients detecting using multiplex RT-PCR were positive, but it were analyzed using Duo ELISA only 22 serum sera positive IgM and IgG from 36 sera. . The Phylogenetic analysis indicates that the isolates from 2011 to 2012 close related with dengue isolate from 1998 and belong to 2009 to 2020.In this study it indicates that DENV 2 predominantly is the cause of DSS.

scholarly journals Differential Expression of Human MicroRNAs During Dengue Virus Infection in THP-1 Monocytes

2021 ◽  
Vol 11 ◽  
Author(s):  
Átila Duque Rossi ◽  
Luiza Mendonça Higa ◽  
Alice Laschuk Herlinger ◽  
Marcelo Ribeiro-Alves ◽  
Mariane Talon de Menezes ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Differential Expression ◽  
Cellular Response ◽  
Clinical Manifestations ◽  
Hemorrhagic Fever ◽  
Denv Infection ◽  
Proinflammatory Response ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Wide Range

Dengue virus (DENV) is the most widespread arbovirus, responsible for a wide range of clinical manifestations, varying from self-limited illness to severe hemorrhagic fever. Dengue severity is associated with host intense proinflammatory response and monocytes have been considered one of the key cell types involved in the early steps of DENV infection and immunopathogenesis. To better understand cellular mechanisms involved in monocyte infection by DENV, we analyzed the expression levels of 754 human microRNAs in DENV-infected THP-1 cells, a human monocytic cell line. Eleven human microRNAs showed differential expression after DENV infection and gene ontology and enrichment analysis revealed biological processes potentially affected by these molecules. Five downregulated microRNAs were significantly linked to cellular response to stress, four to cell death/apoptosis, two to innate immune responses and one upregulated to vesicle mediated, TGF-β signaling, phosphatidylinositol mediated signaling, lipid metabolism process and blood coagulation.

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