scholarly journals Dengue and the Lectin Pathway of the Complement System

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1219
Author(s):  
Romchat Kraivong ◽  
Nuntaya Punyadee ◽  
M. Kathryn Liszewski ◽  
John P. Atkinson ◽  
Panisadee Avirutnan
Keyword(s):  
Complement System ◽  
Complement Activation ◽  
Tissue Injury ◽  
Nonstructural Protein ◽  
Hemorrhagic Fever ◽  
Severe Dengue ◽  
Lectin Pathway ◽  
Target Cells ◽  
Dengue Disease ◽  
Nonstructural Protein 1

Dengue is a mosquito-borne viral disease causing significant health and economic burdens globally. The dengue virus (DENV) comprises four serotypes (DENV1-4). Usually, the primary infection is asymptomatic or causes mild dengue fever (DF), while secondary infections with a different serotype increase the risk of severe dengue disease (dengue hemorrhagic fever, DHF). Complement system activation induces inflammation and tissue injury, contributing to disease pathogenesis. However, in asymptomatic or primary infections, protective immunity largely results from the complement system’s lectin pathway (LP), which is activated through foreign glycan recognition. Differences in N-glycans displayed on the DENV envelope membrane influence the lectin pattern recognition receptor (PRR) binding efficiency. The important PRR, mannan binding lectin (MBL), mediates DENV neutralization through (1) a complement activation-independent mechanism via direct MBL glycan recognition, thereby inhibiting DENV attachment to host target cells, or (2) a complement activation-dependent mechanism following the attachment of complement opsonins C3b and C4b to virion surfaces. The serum concentrations of lectin PRRs and their polymorphisms influence these LP activities. Conversely, to escape the LP attack and enhance the infectivity, DENV utilizes the secreted form of nonstructural protein 1 (sNS1) to counteract the MBL effects, thereby increasing viral survival and dissemination.

scholarly journals Quantitative NS1 antigen and the severity of dengue virus infections

2015 ◽  
Vol 55 (2) ◽  
pp. 87
Author(s):  
Ni Made Adi Purnami ◽  
Mohammad Juffrie ◽  
Made Gde Dwi Lingga Utama
Keyword(s):  
Clinical Course ◽  
Nonstructural Protein ◽  
Dengue Infection ◽  
Hemorrhagic Fever ◽  
Cross Sectional Study ◽  
Severe Dengue ◽  
Virus Infections ◽  
Cross Sectional ◽  
Nonstructural Protein 1 ◽  
Spearman Test

Background Dengue infection is one of the main cause ofmorbidity and mortality in children in Indonesia. Since it is knownthat earlier treatment and supportive therapies can decreased casefatality rate from dengue hemorrhagic fever (DHF), identificationof children who have risks to develop to DHF must be quicklyidentified, mainly in areas of endemic.Objective To find a correlation between increased quantitativesecreted nonstructural protein-1 (sNS1) with clinical course ofsevere dengue infections.Methods This was a cross-sectional study conducted on childrenwith dengue infections in Tropical Infections Division of ChildHealth Department, Sanglah Hospital, Denpasar. Detection ofthe dengue antigen was made by examining sNS1 quantitativeimmuno-assay. Analysis correlation of Spearman test was used tolook the relationship between increased quantitative sNS1 withclinical course of severe dengue infections.Results There was a positive relationship between quantitativesNS1 and clinical course of severe dengue infections with a valueof r = 0.903, P=0.001. Increased sNS1 level had a positivecorrelation with more severe dengue infections.Conclusions Quantitative sNS1 titer has a strong positivecorrelation with clinical course of severe dengue infections.

scholarly journals Viral Toxin NS1 Implication in Dengue Pathogenesis Making It a Pivotal Target in Development of Efficient Vaccine

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 946
Author(s):  
Grégorie Lebeau ◽  
Alisé Lagrave ◽  
Eva Ogire ◽  
Lauriane Grondin ◽  
Soundary Seriacaroupin ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Current Knowledge ◽  
Nonstructural Protein ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Public Health Problem ◽  
Severe Dengue ◽  
Global Public Health ◽  
Dengue Disease ◽  
Nonstructural Protein 1

The mosquito-borne viral disease dengue is a global public health problem causing a wide spectrum of clinical manifestations ranging from mild dengue fever to severe dengue with plasma leakage and bleeding which are often fatal. To date, there are no specific medications to treat dengue and prevent the risk of hemorrhage. Dengue is caused by one of four genetically related but antigenically distinct serotypes DENV-1–DENV-4. The growing burden of the four DENV serotypes has intensified both basic and applied research to better understand dengue physiopathology. Research has shown that the secreted soluble hexameric form of DENV nonstructural protein-1 (sNS1) plays a significant role in the pathogenesis of severe dengue. Here, we provide an overview of the current knowledge about the role of sNS1 in the immunopathogenesis of dengue disease. We discuss the potential use of sNS1 in future vaccine development and its potential to improve dengue vaccine efficiency, particularly against severe dengue illness.

scholarly journals Viral Toxin ns1 as Pivotal Target in Development of Efficient Dengue Vaccine

2021 ◽  
Author(s):  
Grégorie Lebeau ◽  
Alisé Lagrave ◽  
Eva Ogire ◽  
Lauriane Grondin ◽  
Soundary Seriacaroupin ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Nonstructural Protein ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Public Health Problem ◽  
Severe Dengue ◽  
Global Public Health ◽  
Dengue Vaccine ◽  
Dengue Disease ◽  
Nonstructural Protein 1

Mosquito-borne viral disease dengue is a global public health problem causing a wide spectrum of clinical manifestations ranging from mild dengue fever to severe dengue with plasma leakage and bleeding which are often associated to fatality. To date, there are no specific medications to treat dengue and prevent the risk of hemorrhage. Dengue is caused by one of the four related antigenically distinct serotypes, DENV-1 to DENV-4. The growing burden that represents the four DENV serotypes has intensified both basic and applied researches to better understand the dengue physiopathology. It has been proposed a significant role for the secreted soluble DENV nonstructural protein 1 (sNS1) glycoprotein in the pathogenesis of severe dengue. Here, we provided an overview on current knowledge about the role of sNS1 in the immunopathogenesis of dengue disease. The reasons for the consideration of sNS1 in the design of future dengue vaccine candidates will be discussed.

scholarly journals The Good, the Bad, and the Shocking: The Multiple Roles of Dengue Virus Nonstructural Protein 1 in Protection and Pathogenesis

2018 ◽  
Vol 5 (1) ◽  
pp. 227-253 ◽  
Author(s):  
Dustin R. Glasner ◽  
Henry Puerta-Guardo ◽  
P. Robert Beatty ◽  
Eva Harris
Keyword(s):  
Dengue Virus ◽  
Nonstructural Protein ◽  
Direct Action ◽  
Adaptive Immune Response ◽  
Denv Infection ◽  
Multiple Roles ◽  
Severe Dengue ◽  
Potential Contribution ◽  
Dengue Disease ◽  
Nonstructural Protein 1

Dengue virus (DENV) is the most prevalent medically important mosquito-borne virus in the world. Upon DENV infection of a host cell, DENV nonstructural protein 1 (NS1) can be found intracellularly as a monomer, associated with the cell surface as a dimer, and secreted as a hexamer into the bloodstream. NS1 plays a variety of roles in the viral life cycle, particularly in RNA replication and immune evasion of the complement pathway. Over the past several years, key roles for NS1 in the pathogenesis of severe dengue disease have emerged, including direct action of the protein on the vascular endothelium and triggering release of vasoactive cytokines from immune cells, both of which result in endothelial hyperpermeability and vascular leak. Importantly, the adaptive immune response generates a robust response against NS1, and its potential contribution to dengue vaccines is also discussed.

scholarly journals Functional Analyses of the Three Simian Hemorrhagic Fever Virus Nonstructural Protein 1 Papain-Like Proteases

2014 ◽  
Vol 88 (16) ◽  
pp. 9129-9140 ◽  
Author(s):  
H. A. Vatter ◽  
H. Di ◽  
E. F. Donaldson ◽  
G. U. Radu ◽  
T. R. Maines ◽  
...  
Keyword(s):  
Nonstructural Protein ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
Simian Hemorrhagic Fever Virus ◽  
Hemorrhagic Fever Virus ◽  
Nonstructural Protein 1 ◽  
Functional Analyses

scholarly journals Recent Advances in DENV Receptors

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Shuyu Fang ◽  
Yanhua Wu ◽  
Na Wu ◽  
Jing Zhang ◽  
Jing An
Keyword(s):  
Endothelial Cells ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Infection Risk ◽  
Target Cells ◽  
Virus Binding ◽  
Dengue Disease ◽  
High Infection ◽  
Key Factor ◽  
Serious Disease

Dengue is an old disease caused by the mosquito-borne dengue viruses (DENVs), which have four antigenically distinct serotypes (DENV1–4). Infection by any of them can cause dengue fever (DF) and/or a more serious disease, that is, dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). In recent decades, incidence of dengue disease has increased 30-fold, putting a third to half of the world’s population living in dengue-endemic areas at high infection risk. However, the pathogenesis of the disease is still poorly understood. The virus binding with its host cell is not only a first and critical step in their replication cycle but also a key factor for the pathogenicity. In recent years, there have been significant advances in understanding interactions of DENVs with their target cells such as dendritic cells (DC), macrophages, endothelial cells, and hepatocytes. Although DENVs reportedly attach to a variety of receptors on these cells, consensus DENV receptors have not been defined. In this review, we summarize receptors for DENVs on different cells identified in recent years.

scholarly journals Dengue Immunopathogenesis: A Crosstalk between Host and Viral Factors Leading to Disease: PART II - DENV Infection, Adaptive Immune Responses, and NS1 Pathogenesis

2020 ◽  
Author(s):  
Henry Puerta-Guardo ◽  
Scott B. Biering ◽  
Eva Harris ◽  
Norma Pavia-Ruz ◽  
Gonzalo Vázquez-Prokopec ◽  
...  
Keyword(s):  
Immune Responses ◽  
Nonstructural Protein ◽  
Severe Disease ◽  
Critical Role ◽  
Denv Infection ◽  
Severe Dengue ◽  
Adaptive Immune Responses ◽  
Dengue Disease ◽  
Adaptive Immune ◽  
Monocytes And Macrophages

Severe disease is associated with serial infection with DENV of different serotypes. Thus, primary DENV infections normally cause asymptomatic infections, and secondary heterotypic infections with a new DENV serotype potentially increase the risks of developing severe disease. Despite many proposed hypotheses trying to explain it, the exact immunological mechanism leading to severe dengue disease is unknown. In turn, severe manifestations are believed to be a consequence of the combinations of many immunopathogenic mechanisms involving viral and host factors leading to increased pathogenesis and disease. Of these mechanisms, the adaptive immune response has been proposed to play a critical role in the development of severe dengue manifestations. This includes the effect of non-neutralizing but enhancing antibodies produced during primary infections, which results in enhanced-DENV infection of Fc-γ-receptor-expressing cells (e.g. monocytes and macrophages) during DENV heterotypic exposure in a phenomenon called antibody-dependent enhancement (ADE); the increased activation of memory T cells during secondary infections, which has low affinity for the current infecting serotype and high affinity for a past infection with a different serotype known as the original antigenic sin; the unbalanced production of pro-inflammatory cytokines that have a direct effect on vascular endothelial cells resulting in plasma leak in a phenomenon known as cytokine storm; and the excessive activation of the complement system that causes exacerbated inflammatory responses, increasing disease severity. In addition to the adaptive immune responses, a secreted viral factor known as the nonstructural protein 1 (NS1) has been recently proposed as the missing corner piece of the DENV pathogenesis influencing disease. This Part II of the chapter will discuss the interplay between the distinct host adaptive immune responses and viral factors that together contribute to the development of DENV pathogenesis and severe disease.

scholarly journals Complement (C3, C4) and C-reactive Protein Responses to Cardiopulmonary Bypass and Protamine Administration

1993 ◽  
Vol 21 (1) ◽  
pp. 50-55 ◽  
Author(s):  
M. Tulunay ◽  
S. Demiralp ◽  
S. Tastan ◽  
H. Akalin ◽  
U. Ozyurda ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Complement System ◽  
Complement Activation ◽  
Heart Surgery ◽  
Tissue Injury ◽  
Open Heart Surgery ◽  
Complement C3 ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Protamine Administration

Complement activation has been deemed responsible for the damaging effects of cardiopulmonary bypass (CPB) in patients undergoing open heart surgery. We studied C3, C4 and C-reactive protein (CRP) in 22 patients undergoing CPB. In Group 1 (11 patients), protamine was given intravenously and in Group 2 (11 patients), via the aortic root after CPB. Significant decreases were observed in C3 and C4 during CPB in both groups indicating complement activation primarily by the classic pathway. Protamine did not lead to further activation of the complement system. In both groups, C3 levels gradually returned toward baseline within 24 hours but C4 levels were still lower than baseline 24 hours postoperatively. CPB and protamine administration did not cause any significant changes in CRP levels, but CRP increased abruptly 24 hours after operation. Although activation of complement system during CPB is expected to invoke an acute phase response, we conclude that this period is not long enough to induce an increased production of CRP in response to tissue injury or inflammation.

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 A Critical Role for Perivascular Cells in Amplifying Vascular Leakage Induced by Dengue Virus Nonstructural Protein 1

mSphere ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Yin P. Cheung ◽  
Valeria Mastrullo ◽  
Davide Maselli ◽  
Teemapron Butsabong ◽  
Paolo Madeddu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Dengue Virus ◽  
Nonstructural Protein ◽  
Critical Role ◽  
Vascular Leakage ◽  
World Health ◽  
Severe Dengue ◽  
Perivascular Cells ◽  
Nonstructural Protein 1

ABSTRACT Dengue is the most prevalent arthropod-borne viral disease affecting humans, with severe dengue typified by potentially fatal microvascular leakage and hypovolemic shock. Blood vessels of the microvasculature are composed of a tubular structure of endothelial cells ensheathed by perivascular cells (pericytes). Pericytes support endothelial cell barrier formation and maintenance through paracrine and contact-mediated signaling and are critical to microvascular integrity. Pericyte dysfunction has been linked to vascular leakage in noncommunicable pathologies such as diabetic retinopathy but has never been linked to infection-related vascular leakage. Dengue vascular leakage has been shown to result in part from the direct action of the secreted dengue virus (DENV) nonstructural protein NS1 on endothelial cells. Using primary human vascular cells, we show here that NS1 also causes pericyte dysfunction and that NS1-induced endothelial hyperpermeability is more pronounced in the presence of pericytes. Notably, NS1 specifically disrupted the ability of pericytes to support endothelial cell function in a three-dimensional (3D) microvascular assay, with no effect on pericyte viability or physiology. These effects are mediated at least in part through contact-independent paracrine signals involved in endothelial barrier maintenance by pericytes. We therefore identify a role for pericytes in amplifying NS1-induced microvascular hyperpermeability in severe dengue and thus show that pericytes can play a critical role in the etiology of an infectious vascular leakage syndrome. These findings open new avenues of research for the development of drugs and diagnostic assays for combating infection-induced vascular leakage, such as severe dengue. IMPORTANCE The World Health Organization considers dengue one of the top 10 global public health problems. There is no specific antiviral therapy to treat dengue virus and no way of predicting which patients will develop potentially fatal severe dengue, typified by vascular leakage and circulatory shock. We show here that perivascular cells (pericytes) amplify the vascular leakage-inducing effects of the dengue viral protein NS1 through contact-independent signaling to endothelial cells. While pericytes are known to contribute to noncommunicable vascular leakage, this is the first time these cells have been implicated in the vascular effects of an infectious disease. Our findings could pave the way for new therapies and diagnostics to combat dengue and potentially other infectious vascular leakage syndromes.

Sign in / Sign up

Export Citation Format

Share Document