scholarly journals Dengue Immunopathogenesis: A Crosstalk between Host and Viral Factors Leading to Disease: Part I - Dengue Virus Tropism, Host Innate Immune Responses, and Subversion of Antiviral Responses

2020 ◽  
Author(s):  
Henry Puerta-Guardo ◽  
Scott B. Biering ◽  
Eva Harris ◽  
Norma Pavia-Ruz ◽  
Gonzalo Vázquez-Prokopec ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Nonstructural Protein ◽  
Secondary Infection ◽  
Hypovolemic Shock ◽  
Clinical Manifestations ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Innate Immune ◽  
Vascular Leak ◽  
Dengue Disease

Dengue is the most prevalent emerging mosquito-borne viral disease, affecting more than 40% of the human population worldwide. Many symptomatic dengue virus (DENV) infections result in a relatively benign disease course known as dengue fever (DF). However, a small proportion of patients develop severe clinical manifestations, englobed in two main categories known as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Secondary infection with any of the four dengue virus serotypes (DENV1, -2, -3, and -4) is a risk factor to develop severe forms of dengue disease. DSS is primarily characterized by sudden and abrupt endothelial dysfunction, resulting in vascular leak and organ impairment, which may progress to hypovolemic shock and death. Severe DENV disease (DHF/DSS) is thought to follow a complex relationship between distinct immunopathogenic processes involving host and viral factors, such as the serotype cross-reactive antibody-dependent enhancement (ADE), the activation of T cells and complement pathways, the phenomenon of the cytokine storm, and the newly described viral toxin activity of the nonstructural protein 1 (NS1), which together play critical roles in inducing vascular leak and virus pathogenesis. In this chapter that is divided in two parts, we will outline the recent advances in our understanding of DENV pathogenesis, highlighting key viral-host interactions and discussing how these interactions may contribute to DENV immunopathology and the development of vascular leak, a hallmark of severe dengue. Part I will address the general features of the DENV complex, including the virus structure and genome, epidemiology, and clinical outcomes, followed by an updated review of the literature describing the host innate immune strategies as well as the viral mechanisms acting against and in favor of the DENV replication cycle and 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 Common marmoset (Callithrix jacchus) as a primate model of dengue virus infection: development of high levels of viraemia and demonstration of protective immunity

2011 ◽  
Vol 92 (10) ◽  
pp. 2272-2280 ◽  
Author(s):  
Tsutomu Omatsu ◽  
Meng Ling Moi ◽  
Takanori Hirayama ◽  
Tomohiko Takasaki ◽  
Shinichiro Nakamura ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Secondary Infection ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Callithrix Jacchus ◽  
Lymphoid Organs ◽  
Structural Protein ◽  
Primate Model ◽  
Common Marmosets ◽  
Wide Range

Dengue virus (DENV) causes a wide range of illnesses in humans: dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Animal models that constantly develop high levels of viraemia are required for the development of protective and preventive measures. Common marmosets (Callithrix jacchus) demonstrated high levels of viraemia after inoculation with clinical isolates of four serotypes of DENV; in particular, over 106 genome copies ml−1 after inoculation with DENV-2. Non-structural protein 1 and DENV-specific IgM and IgG antibodies were consistently detected. The DENV-2 genome was detected in lymphoid organs including the lymph nodes, spleen and thymus, and also in non-lymphoid organs. DENV antigen was detected by immunohistochemistry in the liver and spleen from inoculated marmosets. Four marmosets were reinoculated with DENV-2 at 33 weeks after primary inoculation with DENV-2. The DENV-2 genome was not detected in any of these marmosets, indicating protection from a secondary infection. The results indicate that common marmosets are highly sensitive to DENV infection, and suggest that marmosets could be a reliable primate model for the evaluation of candidate vaccines.

scholarly journals Manifestation of thrombocytopenia in dengue-2-virus-infected mice

2000 ◽  
Vol 81 (9) ◽  
pp. 2177-2182 ◽  
Author(s):  
Kao-Jean Huang ◽  
Shu-Yi J. Li ◽  
Shiour-Ching Chen ◽  
Hsiao-Sheng Liu ◽  
Yee-Shin Lin ◽  
...  
Keyword(s):  
Virus Infection ◽  
Dengue Virus ◽  
Secondary Infection ◽  
Clinical Manifestations ◽  
Dengue Shock Syndrome ◽  
Dengue Virus Infection ◽  
Platelet Antibody

Dengue virus infection causes dengue fever, dengue haemorrhagic fever and dengue shock syndrome. No animal model is available that mimics these clinical manifestations. In this study, the establishment is reported of a murine model for dengue virus infection that resembles the thrombocytopenia manifestation. Dengue-2 virus (dengue virus type 2) can infect murine cells either in vitro (primary cell culture) or in vivo. Viraemia detected by RT–PCR was found transiently at 2 days after intravenous injection of dengue-2 virus. Transient thrombocytopenia developed at 10–13 days after primary or secondary infection. Anti-platelet antibody was generated after dengue-2 virus infection. There was strain variation in dengue-2 virus infection; the A/J strain was more sensitive than BALB/c or B6 mice. This dengue-2-virus-infected mouse system accompanied by thrombocytopenia and anti-platelet antibody will be a valuable model to study the pathogenicity of dengue virus 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 Progress in the Identification of Dengue Virus Entry/Fusion Inhibitors

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Carolina De La Guardia ◽  
Ricardo Lleonart
Keyword(s):  
Dengue Virus ◽  
Dengue Fever ◽  
Viral Entry ◽  
Virus Entry ◽  
Clinical Manifestations ◽  
Dengue Shock Syndrome ◽  
Initial Step ◽  
Effective Vaccine ◽  
Dengue Disease ◽  
Virus Entry Inhibitors

Dengue fever, a reemerging disease, is putting nearly 2.5 billion people at risk worldwide. The number of infections and the geographic extension of dengue fever infection have increased in the past decade. The disease is caused by the dengue virus, a flavivirus that uses mosquitosAedessp. as vectors. The disease has several clinical manifestations, from the mild cold-like illness to the more serious hemorrhagic dengue fever and dengue shock syndrome. Currently, there is no approved drug for the treatment of dengue disease or an effective vaccine to fight the virus. Therefore, the search for antivirals against dengue virus is an active field of research. As new possible receptors and biological pathways of the virus biology are discovered, new strategies are being undertaken to identify possible antiviral molecules. Several groups of researchers have targeted the initial step in the infection as a potential approach to interfere with the virus. The viral entry process is mediated by viral proteins and cellular receptor molecules that end up in the endocytosis of the virion, the fusion of both membranes, and the release of viral RNA in the cytoplasm. This review provides an overview of the targets and progress that has been made in the quest for dengue virus entry inhibitors.

scholarly journals Elevated Dengue Virus Nonstructural Protein 1 Serum Levels and Altered Toll-Like Receptor 4 Expression, Nitric Oxide, and Tumor Necrosis Factor Alpha Production in Dengue Hemorrhagic Fever Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Denise Maciel Carvalho ◽  
Fernanda Gonçalves Garcia ◽  
Ana Paula Sarreta Terra ◽  
Ana Cristina Lopes Tosta ◽  
Luciana de Almeida Silva ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Clinical Outcomes ◽  
Nonstructural Protein ◽  
Hemorrhagic Fever ◽  
Serum Levels ◽  
Innate Immune ◽  
Necrosis Factor Alpha ◽  
Immune Parameters ◽  
Nonstructural Protein 1 ◽  
Factor Alpha

Background. During dengue virus (DV) infection, monocytes produce tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) which might be critical to immunopathogenesis. Since intensity of DV replication may determine clinical outcomes, it is important to know the effects of viral nonstructural protein 1 (NS1) on innate immune parameters of infected patients. The present study investigates the relationships between dengue virus nonstructural protein 1 (NS1) serum levels and innate immune response (TLR4 expression and TNF-α/NO production) of DV infected patients presenting different clinical outcomes.Methodology/Principal Findings. We evaluated NO, NS1 serum levels (ELISA), TNF-αproduction by peripheral blood mononuclear cells (PBMCs), and TLR4 expression on CD14+cells from 37 dengue patients and 20 healthy controls. Early in infection, increased expression of TLR4 in monocytes of patients with dengue fever (DF) was detected compared to patients with dengue hemorrhagic fever (DHF). Moreover, PBMCs of DHF patients showed higher NS1 and lower NO serum levels during the acute febrile phase and a reduced response to TLR4 stimulation by LPS (with a reduced TNF-αproduction) when compared to DF patients.Conclusions/Significance. During DV infection in humans, some innate immune parameters change, depending on the NS1 serum levels, and phase and severity of the disease which may contribute to development of different clinical outcomes.

scholarly journals Cells in Dengue Virus Infection In Vivo

2010 ◽  
Vol 2010 ◽  
pp. 1-15 ◽  
Author(s):  
Sansanee Noisakran ◽  
Nattawat Onlamoon ◽  
Pucharee Songprakhon ◽  
Hui-Mien Hsiao ◽  
Kulkanya Chokephaibulkit ◽  
...  
Keyword(s):  
Virus Infection ◽  
Dengue Virus ◽  
Emerging Infectious Diseases ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Severe Dengue ◽  
Dengue Virus Infection ◽  
Dengue Disease

Dengue has been recognized as one of the most important vector-borne emerging infectious diseases globally. Though dengue normally causes a self-limiting infection, some patients may develop a life-threatening illness, dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). The reason why DHF/DSS occurs in certain individuals is unclear. Studies in the endemic regions suggest that the preexisting antibodies are a risk factor for DHF/DSS. Viremia and thrombocytopenia are the key clinical features of dengue virus infection in patients. The amounts of virus circulating in patients are highly correlated with severe dengue disease, DHF/DSS. Also, the disturbance, mainly a transient depression, of hematological cells is a critical clinical finding in acute dengue patients. However, the cells responsible for the dengue viremia are unresolved in spite of the intensive efforts been made. Dengue virus appears to replicate and proliferate in many adapted cell lines, but these in vitro properties are extremely difficult to be reproduced in primary cells or in vivo. This paper summarizes reports on the permissive cells in vitro and in vivo and suggests a hematological cell lineage for dengue virus infection in vivo, with the hope that a new focus will shed light on further understanding of the complexities of dengue disease.

scholarly journals High Circulating Levels of the Dengue Virus Nonstructural Protein NS1 Early in Dengue Illness Correlate with the Development of Dengue Hemorrhagic Fever

2002 ◽  
Vol 186 (8) ◽  
pp. 1165-1168 ◽  
Author(s):  
Daniel H. Libraty ◽  
Paul R. Young ◽  
Darren Pickering ◽  
Timothy P. Endy ◽  
Siripen Kalayanarooj ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Dengue Hemorrhagic Fever ◽  
Nonstructural Protein ◽  
Hemorrhagic Fever ◽  
Circulating Levels

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 Obesity as a risk factor for dengue shock syndrome in children

2013 ◽  
Vol 53 (4) ◽  
pp. 187 ◽  
Author(s):  
Maria Mahdalena Tri Widiyati ◽  
Ida Safitri Laksanawati ◽  
Endy Paryanto Prawirohartono
Keyword(s):  
Risk Factor ◽  
Viral Infections ◽  
Infection Type ◽  
Secondary Infection ◽  
Univariate Analysis ◽  
Fluid Management ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Control Group ◽  
Case Group

Background Dengue hemorrhagic fever (DHF) leads to highmorbidity and mortality if not be treated properly and promptly.Obesity may play a role in the progression ofDHF to dengue shocksyndrome (DSS) and could be a prognostic factor.Objective To evaluate childhood obesity as a prognostic factorfor DSS.Methods We reviewed medical records of patients with DHFand DSS admitted to Department of Child Health, Dr. SardjitoHospital, Yogyakarta between June 2008 and February 2011.Subjects were aged less than 18 years and fulfilled WHO criteria(1997) for DHF or DSS. The exclusion criteria were the denguefever, a milder form of disease, or other viral infections. Riskfactors for DSS were analyzed by logistic regression analysis.Results Of342 patients who met the inclusion criteria, there were116 DSS patients (33 .9%) as the case group and 226 DHF patients(66.1%) as the control group. Univariate analysis revealed thatrisk factors for DSS were obesity (OR= 1.88; 95%CI 1.01 to3.5 l) ,secondary infection type (OR=0.82; 95%CI 0.41 to 1.63), plasmaleakage with hematocrit increase> 25% (OR=3.42; 95%CI 2.06to 5.65), platelet count < 20,000/μL (OR= l.95; 95%CI 1.20 to3 .16), and inadequate fluid management from prior hospitalization(OR=9.ll; 95% CI 1.13 to 73.66). By multivariate analysis,plasma leakage with hematocrit increase > 25% was associatedwith DSS (OR=2.5 l; 95%CI 1.12 to 5.59), while obesity was notassociated with DSS (OR= l.03; 95%CI 0.32 to3.3 1).Conclusion Obesity is not a risk factor for DSS, while plasmaleakage with hematocrit increase > 25% is associated with DSS.

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