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 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 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 Hantavirus Causing Hemorrhagic Fever with Renal Syndrome Enters from the Apical Surface and Requires Decay-Accelerating Factor (DAF/CD55)

2008 ◽  
Vol 82 (9) ◽  
pp. 4257-4264 ◽  
Author(s):  
Ellen Krautkrämer ◽  
Martin Zeier
Keyword(s):  
Endothelial Cells ◽  
Epithelial Cells ◽  
Cell Surface ◽  
Hemorrhagic Fever ◽  
Hantavirus Infection ◽  
Target Cells ◽  
Apical Surface ◽  
Decay Accelerating Factor ◽  
African Green Monkey Kidney ◽  
Old World

ABSTRACT The Old World hantaviruses, members of the family Bunyaviridae, cause hemorrhagic fever with renal syndrome (HFRS). Transmission to humans occurs via inhalation of aerosols contaminated with the excreta of infected rodents. The viral antigen is detectable in dendritic cells, macrophages, lymphocytes, and, most importantly, microvascular endothelial cells. However, the site and detailed mechanism of entry of HFRS-causing hantaviruses in polarized epithelial cells have not yet been defined. Therefore, this study focused on the entry of the pathogenic hantaviruses Hantaan and Puumala into African green monkey kidney epithelial cells and primary human endothelial cells. The polarized epithelial and endothelial cells were found to be susceptible to hantavirus infection exclusively from the apical surface. Treatment with phosphatidylinositol-specific phospholipase C, which removes glycosylphosphatidylinositol (GPI)-anchored proteins from the cell surface, protects cells from infection, indicating that hantaviruses require a GPI-anchored protein as a cofactor for entry. Decay-accelerating factor (DAF)/CD55 is a GPI-anchored protein of the complement regulatory system and serves as a receptor for attachment to the apical cell surface for a number of viruses. Infection was reduced by the pretreatment of hantaviral particles with human recombinant DAF. Moreover, the treatment of permissive cells with DAF-specific antibody blocked infection. These results demonstrate that the Old World hantaviruses Hantaan and Puumala enter polarized target cells from the apical site and that DAF is a critical cofactor for infection.

scholarly journals Decreased Type I Interferon Production by Plasmacytoid Dendritic Cells Contributes to Severe Dengue

2020 ◽  
Vol 11 ◽  
Author(s):  
Vinit Upasani ◽  
Carolina Scagnolari ◽  
Federica Frasca ◽  
Nikaïa Smith ◽  
Vincent Bondet ◽  
...  
Keyword(s):  
Single Molecule ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Denv Infection ◽  
Type I Interferons ◽  
Severe Dengue ◽  
Type I ◽  
Type I Ifn ◽  
Dengue Disease ◽  
Healthy Donors

The clinical presentation of dengue virus (DENV) infection is variable. Severe complications mainly result from exacerbated immune responses. Type I interferons (IFN-I) are important in antiviral responses and form a crucial link between innate and adaptive immunity. Their contribution to host defense during DENV infection remains under-studied, as direct quantification of IFN-I is challenging. We combined ultra-sensitive single-molecule array (Simoa) digital ELISA with IFN-I gene expression to elucidate the role of IFN-I in a well-characterized cohort of hospitalized Cambodian children undergoing acute DENV infection. Higher concentrations of type I IFN proteins were observed in blood of DENV patients, compared to healthy donors, and correlated with viral load. Stratifying patients for disease severity, we found a decreased expression of IFN-I in patients with a more severe clinical outcome, such as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). This was seen in parallel to a correlation between low IFNα protein concentrations and decreased platelet counts. Type I IFNs concentrations were correlated to frequencies of plasmacytoid DCs, not DENV-infected myloid DCs and correlated inversely with neutralizing anti-DENV antibody titers. Hence, type I IFN produced in the acute phase of infection is associated with less severe outcome of dengue disease.

scholarly journals Serum IL-18 Is a Potential Biomarker for Predicting Severe Dengue Disease Progression

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Josephine Diony Nanda ◽  
Chiau-Jing Jung ◽  
Rahmat Dani Satria ◽  
Ming-Kai Jhan ◽  
Ting-Jing Shen ◽  
...  
Keyword(s):  
Acute Phase ◽  
Disease Onset ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Denv Infection ◽  
Severe Dengue ◽  
Dengue Disease ◽  
Potential Biomarker ◽  
Tnf Α ◽  
Principal Finding

Background. Dengue virus (DENV) infection is the most common arboviral disease that affects tropical and subtropical regions. Based on the clinical hallmarks, the different severities of patients range from mild dengue fever (MDF) to severe dengue diseases (SDDs) and include dengue hemorrhagic fever or dengue shock syndrome. These are commonly associated with cytokine release syndrome (CRS). The types and levels of cytokines/chemokines, which are suppressed or enhanced, are varied, indicating CRS’s pathogenic and host defensive effects. Principal Finding. In this study, we created an integrated and precise multiplex panel of cytokine/chemokine assays based on our literature analysis to monitor dengue CRS. A 24-plex panel of cytokines/chemokines was evaluated to measure the plasma levels of targeting factors in dengue patients with an MDF and SDD diagnosis without or with comorbidities. As identified in sixteen kinds of cytokines/chemokines, ten were significantly ( P < 0.05 ) (10/16) increased, one was significantly ( P < 0.01 ) (1/16) decreased, and five were potentially (5/16) altered in all dengue patients ( n = 30 ) in the acute phase of disease onset. Compared to MDF, the levels of IL-8 (CXCL-8) and IL-18 in SDD were markedly ( P < 0.05 ) increased, accompanied by positively increased IL-6 and TNF-α and decreased IFN-γ and RANTES. With comorbidities, SDD significantly ( P < 0.01 ) portrayed elevated IL-18 accompanied by increased IL-6 and decreased IFN-α2 and IL-12. In addition, decreased platelets were significantly ( P < 0.05 ) associated with increased IL-18. Significance. These results demonstrate an efficient panel of dengue cytokine/chemokine assays used to explore the possible level of CRS during the acute phase of disease onset; also, we are the first to report the increase of IL-18 in severe dengue with comorbidity compared to severe dengue without comorbidity and mild dengue.

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 Pathogenesis of Dengue: Dawn of a New Era

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 1353 ◽  
Author(s):  
Scott B. Halstead
Keyword(s):  
Severe Disease ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Denv Infection ◽  
Severe Dengue ◽  
Structural Protein ◽  
New Era ◽  
Dengue Disease ◽  
Toll Receptor

Dengue virus (DENV) infections of humans were long thought to be self-limited and of low mortality. Beginning in the 1950s, at the time when four different DENVs were discovered, a lethal variant of dengue emerged. Dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) initially observed in Southeast Asia now has spread throughout the world. Two risk factors for DHF/DSS are well-established: severe disease occurs during a second heterotypic DENV infection or during a first DENV infection in infants born to dengue-immune mothers. A large number of hypotheses have been proposed to explain severe dengue disease. As discussed, few of them attempt to explain why severe disease occurs under the two different immunological settings. New experimental evidence has demonstrated that DENV non-structural protein 1 (NS1) is toll-receptor 4 agonist that stimulates primary human myeloid cells to produce the same cytokines observed during the course of severe dengue disease. In addition, NS1 directly damages endothelial cells. These observations have been repeated and extended to an in vivo mouse model. The well-established phenomenon, antibody-dependent enhancement of DENV infection in Fc-receptor-bearing cells, should similarly enhance the production of DENV NS1 in humans, providing a unitary mechanism for severe disease in both immunological settings

scholarly journals DENV NS1 and MMP-9 cooperate to induce vascular leakage by altering endothelial cell adhesion and tight junction

2020 ◽  
Author(s):  
Geng Li ◽  
Pan Pan ◽  
Miaomiao Shen ◽  
Zhenyang Yu ◽  
Weiwei Ge ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tight Junction ◽  
Endothelial Permeability ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Denv Infection ◽  
Vascular Leakage ◽  
Human Endothelial Cells ◽  
Distinct Mechanism ◽  
Mouse Tissues

AbstractDengue virus (DENV) is a mosquito-borne pathogen that causes a spectrum of diseases including life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Vascular leakage is a common clinical crisis in DHF/DSS patients which is closely associated with increased endothelial permeability. The presence of vascular leakage causes hypotension, circulatory failure or disseminated intravascular coagulation as the disease progresses, which can lead to death under such conditions. However, the mechanisms by which DENV infection caused the vascular leakage are not fully understood. This study reveals a distinct mechanism by which DENV induces endothelial permeability and vascular leakage in human endothelial cells and mice tissues. We initially show that DENV2 promotes the matrix metalloproteinase-9 (MMP-9) expression and secretion in DHF patient serum, peripheral blood mononuclear cells (PBMCs) and macrophages, and further reveal that DENV non-structural protein 1 (NS1) induces MMP-9 expression through activating the nuclear factor κB (NF-κB) signaling pathway. Additionally, NS1 inhibits TIMP-1 expression to facilitates the MMP-9 enzymatic activity which alters the adhesion and tight junctions and vascular leakage in human endothelial cells and mouse tissues. Moreover, NS1 recruits MMP-9 to interact with β-catenin and Zona occludins protein-1/2 to degrade the important adhesion and tight junction proteins, thereby inducing endothelial hyperpermeability and vascular leakage in human endothelial cells and mouse tissues. Thus, we reveal that DENV NS1 and MMP-9 cooperatively induce vascular leakage by impairing endothelial cell adhesion and tight junction, and suggest that MMP-9 may serve as a potential target for the treatment of hypovolemia in DSS/DHF patients.Author SummaryDENV is the most common mosquito-transmitted viral pathogen in humans. In general, DENV-infected patients are either asymptomatic or have flu-like symptoms with fever and rash. However, in severe cases of DENV infection, the disease may progress to dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS), the leading causes of morbidity and mortality in school-age children in tropical and subtropical regions. DENV-induced vascular leakage is characterized by enhanced vascular permeability without morphological damage to the capillary endothelium. We found that a distinct mechanism of DENV NS1 and MMP-9 cooperatively induce vascular leakage is the main reason leading to death in severe dengue patients. Also, NS1 recruits MMP-9 to degrade β-catenin, ZO-1, ZO-2 to intervene endothelial hyperpermeability in human endothelial cells and mouse vascular. Finally, we reveal that DENV activating NF-κB signaling pathway induces MMP-9 expression, in patients, mice, PBMC and macrophages though the viral NS1 protein. This study would provide new in signs into the pathogenesis caused by DENV infection, and suggest that MMP-9 may acts as a drug target for the prevention and treatment of DENV-associated diseases.

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 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.

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