-
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 -
Viruses Nov 2023Subgenomic flaviviral RNAs (sfRNAs) are produced during flavivirus infections in both arthropod and vertebrate cells. They are undegraded products originating from the... (Review)
Review
Subgenomic flaviviral RNAs (sfRNAs) are produced during flavivirus infections in both arthropod and vertebrate cells. They are undegraded products originating from the viral 3' untranslated region (3' UTR), a result of the action of the host 5'-3' exoribonuclease, Xrn1, when it encounters specific RNA structures known as Xrn1-resistant RNAs (xrRNAs) within the viral 3' UTR. Dengue viruses generate three to four distinct species of sfRNAs through the presence of two xrRNAs and two dumbbell structures (DBs). The tertiary structures of xrRNAs have been characterized to form a ringlike structure around the 5' end of the viral RNA, effectively inhibiting the activity of Xrn1. The most important role of DENV sfRNAs is to inhibit host antiviral responses by interacting with viral and host proteins, thereby influencing viral pathogenicity, replicative fitness, epidemiological fitness, and transmission. In this review, we aimed to summarize the biogenesis, structures, and functions of DENV sfRNAs, exploring their implications for viral interference.
Topics: Humans; Flavivirus; Dengue Virus; Subgenomic RNA; 3' Untranslated Regions; Nucleic Acid Conformation; RNA, Viral; Dengue
PubMed: 38140548
DOI: 10.3390/v15122306 -
Vector Borne and Zoonotic Diseases... Jun 2023Dengue virus (DENV) can be divided into four serotypes-DENV-1, DENV-2, DENV-3, and DENV-4. In humans, infection leads to dengue fever (DF), dengue hemorrhagic fever,...
Dengue virus (DENV) can be divided into four serotypes-DENV-1, DENV-2, DENV-3, and DENV-4. In humans, infection leads to dengue fever (DF), dengue hemorrhagic fever, and dengue shock syndrome, both widely prevalent in tropical and subtropical regions. In 2019, a severe outbreak of DF occurred in Xishuangbanna, Yunnan province. To investigate the etiology and genotype of the causative agents of this severe dengue outbreak in Xishuangbanna. Between October and November 2019, the sera of patients clinically diagnosed with DF were collected in the first People's Hospital of Xishuangbanna. RNA was extracted from the sera and amplified by RT-PCR with flavivirus primers. Flavivirus-positive sera were then used to inoculate cells (C6/36); viral RNA was extracted from these cells, amplified, and sequenced with DENV E gene-specific primers. Sequence splicing and nucleotide homology genetic evolution analysis were carried out by biological software (DNAStar). Unique mutations in the E genes of isolated DENV were analyzed by SWISS-MODEL and PyMOL. Of the 60 samples collected from DF patients, 39 tested positively with flavivirus primers. The DENV was isolated from 25 of the 39 positive seras, of which 20 showed cytopathic effects (CPE) and 5 were no CPE. In these 25 isolated nucleic acids, 21 strains of DENV-1, 3 strains of DENV-2, and 1 strain of DENV-3 were identified according to the sequence of E protein. In the four unique mutations (D52, Y149, L312, T386), D52 and Y149 in the E protein of DENV-1 were predicted to be exposed on the surface of the prefusion conformation. The 2019 outbreak of DF in Xishuangbanna area of Yunnan Province consists of at least three serotypes of DENV-1, DENV-2, and DENV-3, and the sources of these virus strains are of mixed and complicated origin.
Topics: Humans; Animals; Dengue Virus; Dengue; Phylogeny; China; Disease Outbreaks; Evolution, Molecular; Genotype
PubMed: 37184906
DOI: 10.1089/vbz.2022.0091 -
Viruses Jan 2021Dengue virus (DENV) is the most widespread arthropod-borne virus, with the number and severity of outbreaks increasing worldwide in recent decades. Dengue is caused by...
Dengue virus (DENV) is the most widespread arthropod-borne virus, with the number and severity of outbreaks increasing worldwide in recent decades. Dengue is caused by genetically distinct serotypes, DENV-1-4. Here, we present data on DENV-1, isolated from patients with dengue fever during an outbreak in Senegal and Mali (Western Africa) in 2015-2019, that were analyzed by sequencing the envelope (E) gene. The emergence and the dynamics of DENV-1 in Western Africa were inferred by using maximum likelihood and Bayesian methods. The DENV-1 grouped into a monophyletic cluster that was closely related to those from Southeast Asia. The virus appears to have been introduced directly into Medina Gounass (Suburb of Dakar), Senegal (location probability = 0.301, posterior = 0.76). The introduction of the virus in Senegal occurred around 2014 (95% HPD = 2012.88-2014.84), and subsequently, the virus moved to regions within Senegal (e.g., Louga and Fatick), causing intense outbreaks in the subsequent years. The virus appears to have been introduced in Mali (a neighboring country) after its introduction in Senegal. In conclusion, we present evidence that the outbreak caused by DENV-1 in urban environments in Senegal and Mali after 2015 was caused by a single viral introduction from Asia.
Topics: Bayes Theorem; Dengue; Dengue Virus; Disease Outbreaks; Genetic Variation; Humans; Likelihood Functions; Phylogeography; RNA, Viral; Senegal; Sequence Analysis, DNA; Serogroup
PubMed: 33406660
DOI: 10.3390/v13010057 -
Viruses Jul 2021The four serotypes of the mature dengue virus can display different morphologies, including the compact spherical, the bumpy spherical and the non-spherical clubshape... (Review)
Review
The four serotypes of the mature dengue virus can display different morphologies, including the compact spherical, the bumpy spherical and the non-spherical clubshape morphologies. In addition, the maturation process of dengue virus is inefficient and therefore some partially immature dengue virus particles have been observed and they are infectious. All these viral particles have different antigenicity profiles and thus may affect the type of the elicited antibodies during an immune response. Understanding the molecular determinants and environmental conditions (e.g., temperature) in inducing morphological changes in the virus and how potent antibodies interact with these particles is important for designing effective therapeutics or vaccines. Several techniques, including cryoEM, site-directed mutagenesis, hydrogen-deuterium exchange mass spectrometry, time-resolve fluorescence resonance energy transfer, and molecular dynamic simulation, have been performed to investigate the structural changes. This review describes all known morphological variants of DENV discovered thus far, their surface protein dynamics and the key residues or interactions that play important roles in the structural changes.
Topics: Antibodies, Neutralizing; Antibodies, Viral; Antibody-Dependent Enhancement; Antigenic Variation; Antigens, Viral; Dengue; Dengue Vaccines; Dengue Virus; Humans; Serogroup; Viral Envelope Proteins
PubMed: 34452312
DOI: 10.3390/v13081446 -
Biosensors Mar 2023Every year, the dengue virus and its principal mosquito vector, sp., have caused massive outbreaks, primarily in equatorial countries. The pre-existing techniques... (Review)
Review
Every year, the dengue virus and its principal mosquito vector, sp., have caused massive outbreaks, primarily in equatorial countries. The pre-existing techniques available for dengue detection are expensive and require trained personnel. Graphene and its derivatives have remarkable properties of electrical and thermal conductivity, and are flexible, light, and biocompatible, making them ideal platforms for biosensor development. The incorporation of these materials, along with appropriate nanomaterials, improves the quality of detection methods. Graphene can help overcome the difficulties associated with conventional techniques. In this review, we have given comprehensive details on current graphene-based diagnostics for dengue virus detection. We have also discussed state-of-the-art biosensing technologies and evaluated the advantages and disadvantages of the same.
Topics: Animals; Dengue Virus; Graphite; Biosensing Techniques; Nanostructures
PubMed: 36979561
DOI: 10.3390/bios13030349 -
Methods in Molecular Biology (Clifton,... 2022The four serotypes of dengue virus (DENV), belonging to the genus Flavivirus in the family Flaviviridae, are the leading cause of arboviral diseases in humans. The...
The four serotypes of dengue virus (DENV), belonging to the genus Flavivirus in the family Flaviviridae, are the leading cause of arboviral diseases in humans. The clinical presentations range from dengue fever to dengue hemorrhagic fever and dengue shock syndrome. Despite decades of efforts on developing intervention strategies against DENV, there is no licensed antiviral, and safe and effective vaccines remain challenging. Similar to other flaviviruses, the assembly of DENV particles occurs in the membranes derived from endoplasmic reticulum; immature virions bud into the lumen followed by maturation in the trans-Golgi and transport through the secretary pathway. A unique feature of flavivirus replication is the production of small and slowly sedimenting subviral particles, known as virus-like particles (VLPs). Co-expression of premembrane (prM) and envelope (E) proteins can generate recombinant VLPs, which are biophysically and antigenically similar to infectious virions and have been employed to study the function of prM and E proteins, assembly, serodiagnostic antigens, and vaccine candidates. Previously, we have developed several assays including sucrose cushion ultracentrifugation, sucrose gradient ultracentrifugation, membrane flotation, subcellular fractionation, and glycosidase digestion assay to exploit the interaction between DENV prM and E proteins, membrane association, subcellular localization, glycosylation pattern, and assembly of VLPs and replicon particles. The information derived from these assays have implications to further our understanding of DENV assembly, replication cycle, intervention strategies, and pathogenesis.
Topics: Antibodies, Viral; Dengue Virus; Humans; Membrane Proteins; Sucrose; Viral Matrix Proteins; Virus Assembly
PubMed: 34709636
DOI: 10.1007/978-1-0716-1879-0_6 -
Current Opinion in Virology Aug 2020Dengue virus is a positive sense, single-stranded RNA virus of the Flaviviridae family that causes mild to severe dengue fever in hundreds of millions of people in... (Review)
Review
Dengue virus is a positive sense, single-stranded RNA virus of the Flaviviridae family that causes mild to severe dengue fever in hundreds of millions of people in tropical/subtropical regions of the world each year. Like many other viruses, dengue has evolved strategies to evade the innate immune response of the host to establish infection. Here we provide an overview of the major alterations provoked by dengue in infected cells, that is, oxidative stress, metabolic reprogramming, and antiviral/inflammatory responses. These biological processes are interconnected and coordinated through the anti-oxidant transcription factor Nrf2, which functions at the interface of metabolism and antiviral immunity.
Topics: Animals; Dengue; Dengue Virus; Humans; NF-E2-Related Factor 2; Oxidative Stress
PubMed: 32829129
DOI: 10.1016/j.coviro.2020.07.015 -
Current Medicinal Chemistry 2020To date, there is still no approved anti-dengue agent to treat dengue infection in the market. Although the only licensed dengue vaccine, Dengvaxia is available, its...
To date, there is still no approved anti-dengue agent to treat dengue infection in the market. Although the only licensed dengue vaccine, Dengvaxia is available, its protective efficacy against serotypes 1 and 2 of dengue virus was reported to be lower than serotypes 3 and 4. Moreover, according to WHO, the risk of being hospitalized and having severe dengue increased in seronegative individuals after they received Dengvaxia vaccination. Nevertheless, various studies had been carried out in search of dengue virus inhibitors. These studies focused on the structural (C, prM, E) and non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) of dengue virus as well as host factors as drug targets. Hence, this article provides an overall up-to-date review of the discovery of dengue virus inhibitors that are only targeting the structural and non-structural viral proteins as drug targets.
Topics: Dengue; Dengue Virus; Humans; Viral Nonstructural Proteins
PubMed: 30514185
DOI: 10.2174/0929867326666181204155336 -
Current Opinion in Virology Aug 2020Dengue viruses 1-4 (DENV 1-4) and Zika virus (ZIKV) are closely related flaviviruses transmitted by Aedes mosquitoes that co-circulate in Asia, the Americas, Africa, and... (Review)
Review
Dengue viruses 1-4 (DENV 1-4) and Zika virus (ZIKV) are closely related flaviviruses transmitted by Aedes mosquitoes that co-circulate in Asia, the Americas, Africa, and Oceania. Here, we review recent and historical literature on in vitro experiments, animal models, and clinical and epidemiological studies to describe how the sequence of DENV 1-4 and ZIKV infections modulates subsequent dengue and Zika disease outcome. Overall, we find these interactions are asymmetric. Immunity from a prior DENV infection or a prior ZIKV infection can enhance future severe dengue disease for some DENV serotypes while protecting against other serotypes. Further, prior DENV immunity has not been shown to enhance future uncomplicated or severe Zika and instead appears to be protective. Interestingly, secondary ZIKV infection induces type-specific ZIKV immunity but only generates weakly cross-neutralizing anti-DENV/ZIKV immunity, consistent with risk of future dengue disease. In contrast, secondary DENV infection induces strongly cross-neutralizing antibodies that protect against subsequent severe dengue disease. These immunologic interactions may be explained by differences in virion structure between DENV 1-4 and ZIKV, which modulate thermostability, susceptibility to neutralization, and cell infectivity. Overall, these observations are important for the understanding and prediction of epidemics and the development and evaluation of dengue and Zika vaccines.
Topics: Animals; Dengue; Dengue Virus; Humans; Viral Vaccines; Zika Virus; Zika Virus Infection
PubMed: 32979816
DOI: 10.1016/j.coviro.2020.08.006