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Frontiers in Bioscience (Landmark... Jan 2018Dengue is a mosquito-borne viral disease caused by four antigenically distinct serotypes of Dengue Virus (DENV), namely DENV1-4 and is currently considered the most... (Review)
Review
Dengue is a mosquito-borne viral disease caused by four antigenically distinct serotypes of Dengue Virus (DENV), namely DENV1-4 and is currently considered the most important arthropod-born viral disease in the world. An effective antiviral therapy to treat Dengue Virus infection is still missing and a number of replicative cycle inhibitors are currently under study. Considering the rapid spreading of DENV and the common timeframe required for bringing a new drug on the market, the repurposing of approved drugs used for different diseases to identify novel inhibitors of this pathogen represents an attractive approach for a rapid therapeutic intervention. Herein, we will describe the most recent drug repurposing approaches to fight DENV infection and their implications in antiviral drug-discovery.
Topics: Animals; Antiviral Agents; Dengue; Dengue Virus; Drug Discovery; Drug Repositioning; Humans; Virus Replication
PubMed: 28930586
DOI: 10.2741/4630 -
Journal of Molecular Biology Aug 2016Dengue is the leading mosquito-transmitted viral infection in the world. There are more than 390 million new infections annually; while the majority of infected... (Review)
Review
Dengue is the leading mosquito-transmitted viral infection in the world. There are more than 390 million new infections annually; while the majority of infected individuals are asymptomatic or develop a self-limited dengue fever, up to 1 million clinical cases develop severe manifestations, including dengue hemorrhagic fever and shock syndrome, resulting in ~25,000 deaths annually, mainly in children. Gaps in our understanding of the mechanisms that contribute to dengue infection and immunopathogenesis have hampered the development of vaccines and antiviral agents. Some of these limitations are highlighted by the explosive re-emergence of another arthropod-borne flavivirus-Zika virus-spread by the same vector, the Aedes aegypti mosquito, that also carries dengue, yellow fever and chikungunya viruses. This review will discuss the early virus-host interactions in dengue infection, with emphasis on the interrelationship between oxidative stress and innate immune pathways, and will provide insight as to how lessons learned from dengue research may expedite therapeutic strategies for Zika virus.
Topics: Aedes; Animals; Dengue Virus; Host-Pathogen Interactions; Humans; Immunity, Innate; Oxidative Stress; Zika Virus
PubMed: 27130436
DOI: 10.1016/j.jmb.2016.04.024 -
BMC Infectious Diseases Aug 2021Dengue fever is a mosquito born disease associated with self-limited to life threatening illness. First detected in Senegal in the nineteenth century, and despite its...
BACKGROUND
Dengue fever is a mosquito born disease associated with self-limited to life threatening illness. First detected in Senegal in the nineteenth century, and despite its growing incidence this last decade, significant knowledge gaps exist in our knowledge of genetic diversity of circulating strains. This study highlights the circulating serotypes and genotypes between January 2017 and December 2018 and their spatial and temporal distribution throughout all regions of Senegal.
METHODS
We used 56 dengue virus (DENV) strains for the analysis collected from 11 sampling areas: 39 from all regions of Senegal, and 17 isolates from Thiès, a particular area of the country. Two real time RT-qPCR systems were used to confirm dengue infection and corresponding serotypes. For molecular characterization, CprM gene was sequenced and submitted to phylogenetic analysis for serotypes and genotypes assignment.
RESULTS
Three dengue virus serotypes (DENV-1-3) were detected by all used methods. DENV-3 was detected in 50% (28/56) of the isolates, followed by DENV-1 and DENV-2, each representing 25% (14/56) of the isolates. DENV-3 belongs to genotype III, DENV-1 to genotype V and DENV-2 to Cosmopolitan genotype. Serotype 3 was detected in 7 sampling locations and a co-circulation of different serotypes was observed in Thiès, Fatick and Richard-toll.
CONCLUSIONS
These results emphasize the need of continuous DENV surveillance in Senegal to detect DENV cases, to define circulating serotypes/genotypes and to prevent the spread and the occurrence of severe cases.
Topics: Dengue; Dengue Virus; Humans; Phylogeny; Public Health Surveillance; Senegal; Serogroup; Spatial Analysis
PubMed: 34429064
DOI: 10.1186/s12879-021-06580-z -
Archives of Virology Apr 2021Dengue virus (DV) is a mosquito-borne virus that is endemic to many tropical and subtropical areas. Recently, the annual incidence of DV infection has increased...
Dengue virus (DV) is a mosquito-borne virus that is endemic to many tropical and subtropical areas. Recently, the annual incidence of DV infection has increased worldwide, including in Korea, due to global warming and increased global travel. We therefore sought to characterize the molecular and evolutionary features of DV-1 and DV-4 isolated from Korean overseas travelers. We used phylogenetic analysis based on the full coding region to classify isolates of DV-1 in Korea into genotype I (43251, KP406802), genotype IV (KP406803), and genotype V (KP406801). In addition, we found that strains of DV-4 belonged to genotype I (KP406806) and genotype II (43257). Evidence of positive selection in DV-1 strains was identified in the C, prM, NS2A, and NS5 proteins, whereas DV-4 showed positive selection only in the non-structural proteins NS2A, NS3, and NS5. The substitution rates per site per year were 5.58 × 10 and 6.72 × 10 for DV-1 and DV-4, respectively, and the time of the most recent common ancestor was determined using the Bayesian skyline coalescent method. In this study, the molecular, phylogenetic, and evolutionary characteristics of Korean DV-1 and DV-4 isolates were evaluated for the first time.
Topics: Amino Acid Sequence; Amino Acid Substitution; Base Sequence; Dengue; Dengue Virus; Evolution, Molecular; Genotype; Humans; Phylogeny; RNA, Viral; Republic of Korea; Selection, Genetic; Serogroup; Travel; Viral Proteins
PubMed: 33575893
DOI: 10.1007/s00705-021-04973-8 -
Viruses Jan 2022Flaviviruses such as dengue virus (DENV) and Zika virus (ZIKV) have evolved sophisticated mechanisms to suppress the host immune system. For instance, flavivirus...
Flaviviruses such as dengue virus (DENV) and Zika virus (ZIKV) have evolved sophisticated mechanisms to suppress the host immune system. For instance, flavivirus infections were found to sabotage peroxisomes, organelles with an important role in innate immunity. The current model suggests that the capsid (C) proteins of DENV and ZIKV downregulate peroxisomes, ultimately resulting in reduced production of interferons by interacting with the host protein PEX19, a crucial chaperone in peroxisomal biogenesis. Here, we aimed to explore the importance of peroxisomes and the role of C interaction with PEX19 in the flavivirus life cycle. By infecting cells lacking peroxisomes we show that this organelle is required for optimal DENV replication. Moreover, we demonstrate that DENV and ZIKV C bind PEX19 through a conserved PEX19-binding motif, which is also commonly found in cellular peroxisomal membrane proteins (PMPs). However, in contrast to PMPs, this interaction does not result in the targeting of C to peroxisomes. Furthermore, we show that the presence of C results in peroxisome loss due to impaired peroxisomal biogenesis, which appears to occur by a PEX19-independent mechanism. Hence, these findings challenge the current model of how flavivirus C might downregulate peroxisomal abundance and suggest a yet unknown role of peroxisomes in flavivirus biology.
Topics: Animals; Capsid Proteins; Cell Line; Dengue Virus; Humans; Membrane Proteins; Organelle Biogenesis; Peroxisomes; Protein Interaction Domains and Motifs; Virus Replication; Zika Virus
PubMed: 35215846
DOI: 10.3390/v14020253 -
Viruses Mar 2017The Flaviviridae family comprises a number of human pathogens, which, although sharing structural and functional features, cause diseases with very different outcomes.... (Review)
Review
The Flaviviridae family comprises a number of human pathogens, which, although sharing structural and functional features, cause diseases with very different outcomes. This can be explained by the plurality of functions exerted by the few proteins coded by viral genomes, with some of these functions shared among members of a same family, but others being unique for each virus species. These non-canonical functions probably have evolved independently and may serve as the base to the development of specific therapies for each of those diseases. Here it is discussed what is currently known about the non-canonical roles of dengue virus (DENV) non-structural proteins (NSPs), which may account for some of the effects specifically observed in DENV infection, but not in other members of the Flaviviridae family. This review explores how DENV NSPs contributes to the physiopathology of dengue, evasion from host immunity, metabolic changes, and redistribution of cellular components during infection.
Topics: Dengue Virus; Host-Pathogen Interactions; Humans; Viral Nonstructural Proteins
PubMed: 28335410
DOI: 10.3390/v9030042 -
Frontiers in Cellular and Infection... 2022Dengue virus (DENV) is the most common arbovirus, causing a significant burden on both the economy and global healthcare systems. The virus is transmitted by species of... (Review)
Review
Dengue virus (DENV) is the most common arbovirus, causing a significant burden on both the economy and global healthcare systems. The virus is transmitted by species of mosquitoes as a swarm of closely related virus genomes, collectively referred to as a quasispecies. The level of genomic diversity within this quasispecies varies as DENV moves through various ecological niches within its transmission cycle. Here, the factors that influence the level of DENV quasispecies diversity during the course of infection in the mosquito vectors are reviewed.
Topics: Aedes; Animals; Arboviruses; Dengue Virus; Genome, Viral; Mosquito Vectors
PubMed: 35811685
DOI: 10.3389/fcimb.2022.888804 -
Pakistan Journal of Pharmaceutical... Mar 2015Dengue fever is caused by the mosquito-borne dengue virus (DENV) serotypes 1-4, and is the most common arboviral infection of humans in subtropical and tropical regions... (Review)
Review
Dengue fever is caused by the mosquito-borne dengue virus (DENV) serotypes 1-4, and is the most common arboviral infection of humans in subtropical and tropical regions of the world. Dengue virus infections can present with a spacious range of clinical signs, from a mild feverish illness to a life-threatening shock syndrome. Till now, there is no approved vaccine or drug against this virus. Therefore, there is an urgent need of development of alternative solutions for dengue. Several plant species have been reported with anti-dengue activity. Many herbal/natural drugs, most of which are commonly used as nutritional components, have been used as antiviral, larvicidal, mosquitocidal and mosquito repellents that may be used against dengue. The objective of this review article was to provide current approaches for the treatment and management/prevention of dengue fever by targeting viral proteins involved in replication cycle of the virus and different developmental stages of mosquito.
Topics: Dengue; Dengue Virus; Humans; Insect Repellents; Mosquito Control; Phytotherapy; Virus Replication
PubMed: 25730815
DOI: No ID Found -
European Journal of Medicinal Chemistry Aug 2019Dengue is the most important arthropod-borne viral disease of humans, with more than half of the global population living in at-risk areas. Despite the negative impact... (Review)
Review
Dengue is the most important arthropod-borne viral disease of humans, with more than half of the global population living in at-risk areas. Despite the negative impact on public health, there are no antiviral therapies available, and the only licensed vaccine, Dengvaxia, has been contraindicated in children below nine years of age. In an effort to combat dengue, several small molecules have entered into human clinical trials. Here, we review anti-DENV molecules and their drug targets that have been published within the past five years (2014-2018). Further, we discuss their probable mechanisms of action and describe a role for classes of clinically approved drugs and also an unclassified class of anti-DENV agents. This review aims to enhance our understanding of novel agents and their cognate targets in furthering innovations in the use of small molecules for dengue drug therapies.
Topics: Animals; Antiviral Agents; Biological Products; Cell Line, Tumor; Dengue Virus; Drug Discovery; Humans; Serine Proteinase Inhibitors; Viral Nonstructural Proteins; Virus Replication
PubMed: 31128447
DOI: 10.1016/j.ejmech.2019.05.010 -
Current Opinion in Virology Jun 2015Dengue virus is the causative agent of dengue virus fever. It infects about 400 million people per year and leads to about 21,000 deaths annually. There is available... (Review)
Review
Dengue virus is the causative agent of dengue virus fever. It infects about 400 million people per year and leads to about 21,000 deaths annually. There is available neither a fully successful vaccine nor a successful drug therapy. Some dengue virus serotypes undergo a temperature dependent conformational change from a 'smooth' form at lower temperatures to a 'bumpy' form at temperatures approaching 37°C, the human body temperature. The bumpy structure is less stable and is probably an intermediate in the formation of a fusogenic virus particle.
Topics: Body Temperature; Dengue Virus; Humans; Temperature; Virion
PubMed: 25974180
DOI: 10.1016/j.coviro.2015.04.006