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Clinical Microbiology Reviews Oct 2009Much remains to be learned about the pathogenesis of the different manifestations of dengue virus (DENV) infections in humans. They may range from subclinical infection... (Review)
Review
Much remains to be learned about the pathogenesis of the different manifestations of dengue virus (DENV) infections in humans. They may range from subclinical infection to dengue fever, dengue hemorrhagic fever (DHF), and eventually dengue shock syndrome (DSS). As both cell tropism and tissue tropism of DENV are considered major determinants in the pathogenesis of dengue, there is a critical need for adequate tropism assays, animal models, and human autopsy data. More than 50 years of research on dengue has resulted in a host of literature, which strongly suggests that the pathogenesis of DHF and DSS involves viral virulence factors and detrimental host responses, collectively resulting in abnormal hemostasis and increased vascular permeability. Differential targeting of specific vascular beds is likely to trigger the localized vascular hyperpermeability underlying DSS. A personalized approach to the study of pathogenesis will elucidate the basis of individual risk for development of DHF and DSS as well as identify the genetic and environmental bases for differences in risk for development of severe disease.
Topics: Dengue; Dengue Virus; Humans
PubMed: 19822889
DOI: 10.1128/CMR.00035-09 -
The Journal of Infectious Diseases Mar 2017Infection with any of the 4 dengue virus serotypes results in a diverse range of symptoms, from mild undifferentiated fever to life-threatening hemorrhagic fever and... (Review)
Review
Infection with any of the 4 dengue virus serotypes results in a diverse range of symptoms, from mild undifferentiated fever to life-threatening hemorrhagic fever and shock. Given that dengue virus infection elicits such a broad range of clinical symptoms, early and accurate laboratory diagnosis is essential for appropriate patient management. Virus detection and serological conversion have been the main targets of diagnostic assessment for many years, however cross-reactivity of antibody responses among the flaviviruses has been a confounding issue in providing a differential diagnosis. Furthermore, there is no single, definitive diagnostic biomarker that is present across the entire period of patient presentation, particularly in those experiencing a secondary dengue infection. Nevertheless, the development and commercialization of point-of-care combination tests capable of detecting markers of infection present during different stages of infection (viral nonstructural protein 1 and immunoglobulin M) has greatly simplified laboratory-based dengue diagnosis. Despite these advances, significant challenges remain in the clinical management of dengue-infected patients, especially in the absence of reliable biomarkers that provide an effective prognostic indicator of severe disease progression. This review briefly summarizes some of the complexities and issues surrounding clinical dengue diagnosis and the laboratory diagnostic options currently available.
Topics: Animals; Dengue; Dengue Virus; Early Diagnosis; Humans; Molecular Diagnostic Techniques
PubMed: 28403441
DOI: 10.1093/infdis/jiw649 -
Viruses Jul 2020Dengue, caused by infection of any of four dengue virus serotypes (DENV-1 to DENV-4), is a mosquito-borne disease of major public health concern associated with... (Review)
Review
Dengue, caused by infection of any of four dengue virus serotypes (DENV-1 to DENV-4), is a mosquito-borne disease of major public health concern associated with significant morbidity, mortality, and economic cost, particularly in developing countries. Dengue incidence has increased 30-fold in the last 50 years and over 50% of the world's population, in more than 100 countries, live in areas at risk of DENV infection. We reviews DENV biology, epidemiology, transmission dynamics including circulating serotypes and genotypes, the immune response, the pathogenesis of the disease as well as updated diagnostic methods, treatments, vector control and vaccine developments.
Topics: Aedes; Animals; Dengue; Dengue Vaccines; Dengue Virus; Genome, Viral; Genotype; Humans; Mosquito Control; Mosquito Vectors; Virus Replication
PubMed: 32751561
DOI: 10.3390/v12080829 -
Lancet (London, England) Jan 2015Dengue viruses have spread rapidly within countries and across regions in the past few decades, resulting in an increased frequency of epidemics and severe dengue... (Review)
Review
Dengue viruses have spread rapidly within countries and across regions in the past few decades, resulting in an increased frequency of epidemics and severe dengue disease, hyperendemicity of multiple dengue virus serotypes in many tropical countries, and autochthonous transmission in Europe and the USA. Today, dengue is regarded as the most prevalent and rapidly spreading mosquito-borne viral disease of human beings. Importantly, the past decade has also seen an upsurge in research on dengue virology, pathogenesis, and immunology and in development of antivirals, vaccines, and new vector-control strategies that can positively impact dengue control and prevention.
Topics: Dengue; Dengue Virus; Humans
PubMed: 25230594
DOI: 10.1016/S0140-6736(14)60572-9 -
Current Protocols in Microbiology Nov 2012Dengue is a disease caused by infection with one of the four dengue virus serotypes (DENV-1, -2, -3, and -4). The virus is transmitted to humans by Aedes sp. mosquitoes....
Dengue is a disease caused by infection with one of the four dengue virus serotypes (DENV-1, -2, -3, and -4). The virus is transmitted to humans by Aedes sp. mosquitoes. This enveloped virus contains a positive single-stranded RNA genome. Clinical manifestations of dengue can have a wide range of outcomes varying from a mild febrile illness to a life-threatening condition. New techniques have largely replaced the use of DENV isolation in disease diagnosis. However, virus isolation still serves as the gold standard for detection and serotyping of DENV and is common practice in research and reference laboratories where clinical isolates of the virus are characterized and sequenced, or used for a variety of research experiments. Isolation of DENV from clinical samples can be achieved in mammalian and mosquito cells or by inoculation of mosquitoes. The experimental methods presented here describe the most common procedures used for the isolation, serotyping, propagation, and quantification of DENV.
Topics: Aedes; Animals; Cell Line; Dengue; Dengue Virus; Humans; Preservation, Biological; Virology; Virus Cultivation
PubMed: 23184594
DOI: 10.1002/9780471729259.mc15d02s27 -
PloS One 2016Dengue virus (DENV) infection is currently a major cause of morbidity and mortality in the world; it has become more common and virulent over the past half-century and... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Dengue virus (DENV) infection is currently a major cause of morbidity and mortality in the world; it has become more common and virulent over the past half-century and has gained much attention. Thus, this review compared the percentage of severe cases of both primary and secondary infections with different serotypes of dengue virus.
METHODS
Data related to the number of cases involving dengue fever (DF), dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) or severe dengue infections caused by different serotypes of dengue virus were obtained by using the SCOPUS, the PUBMED and the OVID search engines with the keywords "(dengue* OR dengue virus*) AND (severe dengue* OR severity of illness index* OR severity* OR DF* OR DHF* OR DSS*) AND (serotypes* OR serogroup*)", according to the MESH terms suggested by PUBMED and OVID.
RESULTS
Approximately 31 studies encompassing 15,741 cases reporting on the dengue serotypes together with their severity were obtained, and meta-analysis was carried out to analyze the data. This study found that DENV-3 from the Southeast Asia (SEA) region displayed the greatest percentage of severe cases in primary infection (95% confidence interval (CI), 31.22-53.67, 9 studies, n = 598, I2 = 71.53%), whereas DENV-2, DENV-3, and DENV-4 from the SEA region, as well as DENV-2 and DENV-3 from non-SEA regions, exhibited the greatest percentage of severe cases in secondary infection (95% CI, 11.64-80.89, 4-14 studies, n = 668-3,149, I2 = 14.77-96.20%). Moreover, DENV-2 and DENV-4 from the SEA region had been found to be more highly associated with dengue shock syndrome (DSS) (95% CI, 10.47-40.24, 5-8 studies, n = 642-2,530, I2 = 76.93-97.70%), while DENV-3 and DENV-4 from the SEA region were found to be more highly associated with dengue hemorrhagic fever (DHF) (95% CI, 31.86-54.58, 9 studies, n = 674-2,278, I2 = 55.74-88.47%), according to the 1997 WHO dengue classification. Finally, DENV-2 and DENV-4 from the SEA region were discovered to be more highly associated with secondary infection compared to other serotypes (95% CI, 72.01-96.32, 9-12 studies, n = 671-2,863, I2 = 25.01-96.75%).
CONCLUSION
This study provides evidence that the presence of certain serotypes, including primary infection with DENV-3 from the SEA region and secondary infection with DENV-2, DENV-3, and DENV-4 also from the SEA region, as well as DENV-2 and DENV-3 from non SEA regions, increased the risk of severe dengue infections. Thus, these serotypes are worthy of special consideration when making clinical predictions upon the severity of the infection.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42015026093 (http://www.crd.york.ac.uk/PROSPERO).
Topics: Dengue; Dengue Virus; Humans; Molecular Typing; Recurrence; Serogroup; Severe Dengue; Severity of Illness Index
PubMed: 27213782
DOI: 10.1371/journal.pone.0154760 -
Journal of Biomedical Science Apr 2024Dengue viruses (DENV) are positive-stranded RNA viruses belonging to the Flaviviridae family. DENV is the causative agent of dengue, the most rapidly spreading viral... (Review)
Review
Dengue viruses (DENV) are positive-stranded RNA viruses belonging to the Flaviviridae family. DENV is the causative agent of dengue, the most rapidly spreading viral disease transmitted by mosquitoes. Each year, millions of people contract the virus through bites from infected female mosquitoes of the Aedes species. In the majority of individuals, the infection is asymptomatic, and the immune system successfully manages to control virus replication within a few days. Symptomatic individuals may present with a mild fever (Dengue fever or DF) that may or may not progress to a more critical disease termed Dengue hemorrhagic fever (DHF) or the fatal Dengue shock syndrome (DSS). In the absence of a universally accepted prophylactic vaccine or therapeutic drug, treatment is mostly restricted to supportive measures. Similar to many other viruses that induce acute illness, DENV has developed several ways to modulate host metabolism to create an environment conducive to genome replication and the dissemination of viral progeny. To search for new therapeutic options, understanding the underlying host-virus regulatory system involved in various biological processes of the viral life cycle is essential. This review aims to summarize the complex interaction between DENV and the host cellular machinery, comprising regulatory mechanisms at various molecular levels such as epigenetic modulation of the host genome, transcription of host genes, translation of viral and host mRNAs, post-transcriptional regulation of the host transcriptome, post-translational regulation of viral proteins, and pathways involved in protein degradation.
Topics: Dengue Virus; Humans; Dengue; Animals; Host-Pathogen Interactions; Virus Replication
PubMed: 38649998
DOI: 10.1186/s12929-024-01030-9 -
Biochemical Pharmacology Aug 2018Despite the ever-increasing global incidence of dengue fever, there are no specific chemotherapy regimens for its treatment. Structural studies on dengue virus (DENV)... (Review)
Review
Despite the ever-increasing global incidence of dengue fever, there are no specific chemotherapy regimens for its treatment. Structural studies on dengue virus (DENV) proteins have revealed potential drug targets. Major DENV proteins such as the envelope protein and non-structural (NS) proteins 3 and 5 have been extensively investigated in antiviral studies, but with limited success in vitro. However, the minor NS proteins NS2 and NS4 have remained relatively underreported. Emerging evidence indicating their indispensable roles in virus propagation and host immunomodulation should encourage us to target these proteins for drug discovery. This review covers current knowledge on DENV NS2 and NS4 proteins from structural and functional perspectives and assesses their potential as targets for antiviral design. Antiviral targets in NS2A include surface-exposed transmembrane regions involved in pathogenesis, while those in NS2B include protease-binding sites in a conserved hydrophilic domain. Ideal drug targets in NS4A include helix α4 and the PEPEKQR sequence, which are essential for NS4A-2K cleavage and NS4A-NS4B association, respectively. In NS4B, the cytoplasmic loop connecting helices α5 and α7 is an attractive target for antiviral design owing to its role in dimerization and NS4B-NS3 interaction. Findings implicating NS2A, NS2B, and NS4A in membrane-modulation and viroporin-like activities indicate an opportunity to target these proteins by disrupting their association with membrane lipids. Despite the lack of 3D structural data, recent topological findings and progress in structure-prediction methods should be sufficient impetus for targeting NS2 and NS4 for drug design.
Topics: Amino Acid Sequence; Animals; Dengue; Dengue Virus; Humans; Protein Structure, Secondary; Viral Nonstructural Proteins
PubMed: 29674002
DOI: 10.1016/j.bcp.2018.04.008 -
Cell Mar 2002The first structure of a flavivirus has been determined by using a combination of cryoelectron microscopy and fitting of the known structure of glycoprotein E into the...
The first structure of a flavivirus has been determined by using a combination of cryoelectron microscopy and fitting of the known structure of glycoprotein E into the electron density map. The virus core, within a lipid bilayer, has a less-ordered structure than the external, icosahedral scaffold of 90 glycoprotein E dimers. The three E monomers per icosahedral asymmetric unit do not have quasiequivalent symmetric environments. Difference maps indicate the location of the small membrane protein M relative to the overlaying scaffold of E dimers. The structure suggests that flaviviruses, and by analogy also alphaviruses, employ a fusion mechanism in which the distal beta barrels of domain II of the glycoprotein E are inserted into the cellular membrane.
Topics: Capsid; Cryoelectron Microscopy; Dengue Virus; Humans; Hydrogen-Ion Concentration; Image Processing, Computer-Assisted; Lipid Bilayers; Membrane Fusion; Models, Molecular; Viral Envelope Proteins
PubMed: 11893341
DOI: 10.1016/s0092-8674(02)00660-8 -
Current Medicinal Chemistry 2021Dengue, the oldest and the most prevalent mosquito-borne illness, is caused by the dengue virus (DENV), from the family of Flaviviridae. It infects approximately 400... (Review)
Review
Dengue, the oldest and the most prevalent mosquito-borne illness, is caused by the dengue virus (DENV), from the family of Flaviviridae. It infects approximately 400 million individuals per annum, with approximately half of the global population residing in high-risk areas. The factors attributed to the geographic expansion of dengue, include urbanization, population density, modern means of transportation, international travels, habit modification, climate change, virus genetics, vector capacity, and poor vector control. Despite the significant progress made in the past against dengue, no effective antiviral therapy is currently available. Among the structural and non-structural proteins encoded by DENV genome, the NS2B-NS3 protease complex is amongst the extensively studied targets for the development of antiviral therapeutics owing to its multiple roles in virus life cycle. Furthermore, protease inhibitors were found to be successful in Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV). Likewise, several peptidic, peptide derived/peptidomimetic, and small molecules inhibitors have been identified as DENV protease inhibitors. Unfortunately, none of them have resulted in a clinically approved drug. Considering all the abovementioned facts, this review descriptively explains the molecular mechanism and therapeutic potential of DENV protease along with an up to date information on various competitive inhibitors reported against DENV protease. This review might be helpful for the researchers working in this area to understand the critical aspects of DENV protease that will help them develop effective and novel inhibitors against DENV to protect lives of millions of people worldwide.
Topics: Animals; Antiviral Agents; Dengue Virus; Humans; Peptide Hydrolases; Protease Inhibitors; Serine Endopeptidases; Viral Nonstructural Proteins
PubMed: 34212826
DOI: 10.2174/0929867328666210629152929