scholarly journals Pathogenesis of Dengue virus in Host immune system and its genomic variation

2021 ◽  
Vol 6 (1) ◽  
pp. 16-30
Author(s):  
Sohail Sohail ◽  
Mukarram Farooq ◽  
Fareeha Sohail ◽  
Hamza Rana ◽  
Husnain Karim ◽  
...  
Keyword(s):  
T Cells ◽  
Dengue Virus ◽  
Febrile Illness ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Genomic Variation ◽  
Severe Dengue ◽  
Host Immune System ◽  
Ns1 Protein ◽  
Protein Cleavage

Dengue viruses are the most prevalent arthropod-borne viral diseases in humans, infecting 50-100 million people each year. Its serotypes are the most common causes of arboviral illness, putting half of the world's population at risk of infection. Because there is no vaccine or antiviral medicines, the only way to manage the disease is to reduce the Aedes mosquito vectors. DENV infection can be asymptomatic or cause a self-limiting, acute febrile illness with varying degrees of severity. High fever, headache, stomach discomfort, rash, myalgia, and arthralgia are the typical symptoms of dengue fever (DF). Thrombocytopenia, vascular leakage, and hypotension are symptoms of severe dengue, dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). Systemic shock characterizes DSS, which can be deadly. Dengue virus infection pathogenesis is linked to a complex interaction between virus, host genes, and host immune response. Major drivers of disease vulnerability include host factors such as antibody-dependent enhancement (ADE), memory cross-reactive T cells, anti-DENV NS1 antibodies, autoimmunity, and genetic variables. The NS1 protein and anti-DENV NS1 antibodies were thought to be involved in the development of severe dengue. The progressive infection may change the cytokine response of cross reactive CD4+ T cells. The need for dengue vaccines that can generate strong protective immunity against all four serotypes is required. To create such vaccines, a thorough understanding of DENV adaptive immunity is required. Structural and functional research have shown that the degree of prM protein cleavage as well as the ensemble of conformational states sampled by virions influence DENV sensitivity to antibody-mediated neutralization, which has crucial implications for vaccine formulation.

scholarly journals Current Understanding of the Pathogenesis of Dengue Virus Infection

2020 ◽  
Author(s):  
Puneet Bhatt ◽  
Sasidharan Pillai Sabeena ◽  
Muralidhar Varma ◽  
Govindakarnavar Arunkumar
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Virus Infection ◽  
Dengue Virus ◽  
Genetic Factors ◽  
Host Immune Response ◽  
Severe Dengue ◽  
Ns1 Protein ◽  
Dengue Virus Infection ◽  
Antibody Dependent Enhancement

AbstractThe pathogenesis of dengue virus infection is attributed to complex interplay between virus, host genes and host immune response. Host factors such as antibody-dependent enhancement (ADE), memory cross-reactive T cells, anti-DENV NS1 antibodies, autoimmunity as well as genetic factors are major determinants of disease susceptibility. NS1 protein and anti-DENV NS1 antibodies were believed to be responsible for pathogenesis of severe dengue. The cytokine response of cross-reactive CD4+ T cells might be altered by the sequential infection with different DENV serotypes, leading to further elevation of pro-inflammatory cytokines contributing a detrimental immune response. Fcγ receptor-mediated antibody-dependent enhancement (ADE) results in release of cytokines from immune cells leading to vascular endothelial cell dysfunction and increased vascular permeability. Genomic variation of dengue virus and subgenomic flavivirus RNA (sfRNA) suppressing host immune response are viral determinants of disease severity. Dengue infection can lead to the generation of autoantibodies against DENV NS1antigen, DENV prM, and E proteins, which can cross-react with several self-antigens such as plasminogen, integrin, and platelet cells. Apart from viral factors, several host genetic factors and gene polymorphisms also have a role to play in pathogenesis of DENV infection. This review article highlights the various factors responsible for the pathogenesis of dengue and also highlights the recent advances in the field related to biomarkers which can be used in future for predicting severe disease outcome.

scholarly journals Addition of Partial Envelope Domain II into Envelope Domain III of Dengue Virus Antigen Potentiates the Induction of Virus-Neutralizing Antibodies and Induces Protective Immunity

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 88 ◽  
Author(s):  
Jisang Park ◽  
Hyun-Young Lee ◽  
Ly Tuan Khai ◽  
Nguyen Thi Thu Thuy ◽  
Le Quynh Mai ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Dengue Fever ◽  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Secondary Infection ◽  
Febrile Illness ◽  
Hemorrhagic Fever ◽  
Denv Infection ◽  
Severe Dengue ◽  
Domain Iii

Dengue virus (DENV) comprises four serotypes in the family Flaviviridae and is a causative agent of dengue-related diseases, including dengue fever. Dengue fever is generally a self-limited febrile illness. However, secondary infection of patients with a suboptimal antibody (Ab) response provokes life-threatening severe dengue hemorrhagic fever or dengue shock syndrome. To develop a potent candidate subunit vaccine against DENV infection, we developed the EDII-cEDIII antigen, which contains partial envelope domain II (EDII) including the fusion loop and BC loop epitopes together with consensus envelope domain III (cEDIII) of all four serotypes of DENV. We purified Ab from mice after immunization with EDII-cEDIII or cEDIII and compared their virus neutralization and Ab-dependent enhancement of DENV infection. Anti-EDII-cEDIII Ab showed stronger neutralizing activity and lower Ab-dependent peak enhancement of DENV infection compared with anti-cEDIII Ab. Following injection of Ab-treated DENV into AG129 mice, anti-EDII-cEDIII Ab ameliorated DENV infection in tissues with primary and secondary infection more effectively than anti-cEDIII Ab. In addition, anti-EDII-cEDIII Ab protected against DENV1, 2, and 4 challenge. We conclude that EDII-cEDIII induces neutralizing and protective Abs, and thus, shows promise as a candidate subunit vaccine for DENV infection.

scholarly journals Interferon-Dependent Immunity Is Essential for Resistance to Primary Dengue Virus Infection in Mice, Whereas T- and B-Cell-Dependent Immunity Are Less Critical

2004 ◽  
Vol 78 (6) ◽  
pp. 2701-2710 ◽  
Author(s):  
Sujan Shresta ◽  
Jennifer L. Kyle ◽  
Heidi M. Snider ◽  
Manasa Basavapatna ◽  
P. Robert Beatty ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Dengue Virus ◽  
B Cell ◽  
Severe Disease ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Viral Spread ◽  
Ifn Γ ◽  
Β Receptor

ABSTRACT Dengue virus (DEN) causes dengue fever and dengue hemorrhagic fever/dengue shock syndrome, which are major public health problems worldwide. The immune factors that control DEN infection or contribute to severe disease are neither well understood nor easy to examine in humans. In this study, we used wild-type and congenic mice lacking various components of the immune system to study the immune mechanisms in the response to DEN infection. Our results demonstrate that alpha/beta interferon (IFN-α/β) and IFN-γ receptors have critical, nonoverlapping functions in resolving primary DEN infection. Furthermore, we show that IFN-α/β receptor-mediated action limits initial DEN replication in extraneural sites and controls subsequent viral spread into the central nervous system (CNS). In contrast, IFN-γ receptor-mediated responses seem to act at later stages of DEN disease by restricting viral replication in the periphery and eliminating virus from the CNS. Mice deficient in B, CD4+ T, or CD8+ T cells had no increased susceptibility to DEN; however, RAG mice (deficient in both B and T cells) were partially susceptible to DEN infection. In summary, (i) IFN-α/β is critical for early immune responses to DEN infection, (ii) IFN-γ-mediated immune responses are crucial for both early and late clearance of DEN infection in mice, and (iii) the IFN system plays a more important role than T- and B-cell-dependent immunity in resistance to primary DEN infection in mice.

scholarly journals The Association between Obesity and Severity of Dengue Hemorrhagic Fever in Children at Wangaya General Hospital

2019 ◽  
Vol 7 (15) ◽  
pp. 2444-2446
Author(s):  
Bella Kurnia ◽  
I Wayan Bikin Suryawan
Keyword(s):  
Logistic Regression ◽  
Dengue Virus ◽  
General Hospital ◽  
Dengue Hemorrhagic Fever ◽  
Febrile Illness ◽  
Dengue Shock Syndrome ◽  
Binary Logistic Regression ◽  
Hemorrhagic Fever ◽  
P Value ◽  
Binary Logistic Regression Analysis

BACKGROUND: Dengue is a mosquito-borne disease caused by any one of four closely related Dengue virus (DENV 1-4). The clinical sign Dengue virus infection can vary from mild (mild febrile illness), Dengue Fever (DF), Dengue Hemorrhagic Fever (DHF) to Dengue Hemorrhagic Fever with shock (Dengue Shock Syndrome, DSS). AIM: This study was designed to determine the relationship of obesity with the severity of Dengue Hemorrhagic Fever in children. METHODS: It is a case-control study. The data of patients were retrospectively collected from the Department of Child Health at the Wangaya General Hospital between March 2019 to May 2019. It uses consecutive sampling. The total sample of 22 children with DHF with shock and 22 children with DHF without shock were investigated. Statistical analysis has been performed by SPSS Statistics 20.0 for Mac (IBM Corp., Armonk, New York, USA). DHF positive results were compared by the Chi-square test and binary logistic regression. RESULTS: Prevalence of DHF with shock is fifty per cent's and DHF without shock is 50%. Prevalence of obesity is 40.9%. The result of binary logistic regression analysis of obesity in children and the severity of DHF was significantly correlated with P-value 0.004 and OR = 7.734. CONCLUSION: Obesity is associated with the severity of Dengue Hemorrhagic fever in children.

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 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 Increased frequencies of CD4+CD25high regulatory T cells in acute dengue infection

2007 ◽  
Vol 204 (5) ◽  
pp. 979-985 ◽  
Author(s):  
Kerstin Lühn ◽  
Cameron P. Simmons ◽  
Edward Moran ◽  
Nguyen Thi Phuong Dung ◽  
Tran Nguyen Bich Chau ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Severe Disease ◽  
Acute Infection ◽  
Dengue Infection ◽  
Hemorrhagic Fever ◽  
Severe Dengue ◽  
Effector T Cell ◽  
Cell Effector

Dengue virus infection is an increasingly important tropical disease, causing 100 million cases each year. Symptoms range from mild febrile illness to severe hemorrhagic fever. The pathogenesis is incompletely understood, but immunopathology is thought to play a part, with antibody-dependent enhancement and massive immune activation of T cells and monocytes/macrophages leading to a disproportionate production of proinflammatory cytokines. We sought to investigate whether a defective population of regulatory T cells (T reg cells) could be contributing to immunopathology in severe dengue disease. CD4+CD25highFoxP3+ T reg cells of patients with acute dengue infection of different severities showed a conventional phenotype. Unexpectedly, their capacity to suppress T cell proliferation and to secrete interleukin-10 was not altered. Moreover, T reg cells suppressed the production of vasoactive cytokines after dengue-specific stimulation. Furthermore, T reg cell frequencies and also T reg cell/effector T cell ratios were increased in patients with acute infection. A strong indication that a relative rise of T reg cell/effector T cell ratios is beneficial for disease outcome comes from patients with mild disease in which this ratio is significantly increased (P < 0.0001) in contrast to severe cases (P = 0.2145). We conclude that although T reg cells expand and function normally in acute dengue infection, their relative frequencies are insufficient to control the immunopathology of severe disease.

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.

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