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International Journal of Molecular... Oct 2021The infection of mammalian cells by enveloped viruses is triggered by the interaction of viral envelope glycoproteins with the glycosaminoglycan, heparan sulfate. By...
The infection of mammalian cells by enveloped viruses is triggered by the interaction of viral envelope glycoproteins with the glycosaminoglycan, heparan sulfate. By mimicking this carbohydrate, some anionic polysaccharides can block this interaction and inhibit viral entry and infection. As heparan sulfate carries both carboxyl and sulfate groups, this work focused on the derivatization of a (1→3)(1→6)-β-D-glucan, botryosphaeran, with these negatively-charged groups in an attempt to improve its antiviral activity. Carboxyl and sulfonate groups were introduced by carboxymethylation and sulfonylation reactions, respectively. Three derivatives with the same degree of carboxymethylation (0.9) and different degrees of sulfonation (0.1; 0.2; 0.4) were obtained. All derivatives were chemically characterized and evaluated for their antiviral activity against herpes (HSV-1, strains KOS and AR) and dengue (DENV-2) viruses. Carboxymethylated botryosphaeran did not inhibit the viruses, while all sulfonated-carboxymethylated derivatives were able to inhibit HSV-1. DENV-2 was inhibited only by one of these derivatives with an intermediate degree of sulfonation (0.2), demonstrating that the dengue virus is more resistant to anionic β-D-glucans than the Herpes simplex virus. By comparison with a previous study on the antiviral activity of sulfonated botryosphaerans, we conclude that the presence of carboxymethyl groups might have a detrimental effect on antiviral activity.
Topics: Animals; Antiviral Agents; Cell Survival; Chlorocebus aethiops; Dengue Virus; Glucans; Herpesviridae; Methylation; Sulfonic Acids; Vero Cells; Virus Internalization; beta-Glucans
PubMed: 34681671
DOI: 10.3390/ijms222011013 -
PloS One 2018The role of intra-host genetic diversity in dengue viral populations remains a topic of debate, particularly the impact on transmission of changes in this diversity....
The role of intra-host genetic diversity in dengue viral populations remains a topic of debate, particularly the impact on transmission of changes in this diversity. Several approaches have been taken to increasing and decreasing the genetic diversity of populations of RNA viruses and have drawn what appear to be contradictory conclusions. A 2-6 fold increase in genetic diversity of a wild type population of dengue virus serotype 1(DENV1) and of an infectious clone population derived from the wild type population, produced by treatment with nucleotide analogue 5 fluorouracil (5FU), drove the populations to extinction. Removal of 5FU immediately prior to extinction, resulted in a return to pre-treatment levels of fitness and genetic diversity, albeit with novel single nucleotide polymorphisms. These observations support the concept that DENV populations exist on fitness peaks determined by their transmission requirements and either an increase or a decrease in genetic diversity may result in a loss of fitness.
Topics: Dengue Virus; Fluorouracil; Genes, Viral; Genetic Variation
PubMed: 29293524
DOI: 10.1371/journal.pone.0189554 -
PloS One 2016Dengue used to be recognized as an imported and sporadic disease in China. Since June 2014, an unexpected large dengue outbreak has attacked Guangzhou, China, resulting...
Dengue used to be recognized as an imported and sporadic disease in China. Since June 2014, an unexpected large dengue outbreak has attacked Guangzhou, China, resulting in more than 40,000 cases. Among the 1,942 laboratory-confirmed hospitalized dengue cases, 121 were diagnosed as severe dengue according to the 2009 WHO guideline, and 2 patients finally died. Laboratory diagnosis and virus isolation demonstrated that the majority (96%) cases were caused by dengue virus serotype 1 (DENV-1), and the others by serotype 2 (DENV-2). 14 DENV strains were isolated from the sera of acute-phase dengue patients during this outbreak, and the complete envelope (E) gene of 12 DENV-1 strains and two DENV-2 strains were determined using RT-PCR assay. Phylogenetic analysis based on the E gene revealed the DENV-1 strains isolated during the outbreak belonged to genotype I and V, respectively. These isolates formed three clades. DENV-2 isolates were assigned to the same clade belonging to genotype cosmopolitan. These strains isolated in 2014 were closely related to the isolates obtained from the same province, Guangdong, in 2013. No amino acid mutations known to increase virulence were identified throughout the E protein of isolates in 2014. These results indicate that dengue is turning into endemic in Guangdong, China, and extensive seroepidemiological investigation and mosquito control measures are critically needed in the future.
Topics: Adult; Aged; Aged, 80 and over; China; Dengue; Dengue Virus; Disease Outbreaks; Female; Genome, Viral; Genotype; Humans; Male; Middle Aged; Molecular Epidemiology; Phylogeny; Sequence Analysis, DNA; Serogroup
PubMed: 27257804
DOI: 10.1371/journal.pone.0156548 -
Journal of Vector Borne Diseases Jan 2024Dengue and chikungunya infections are one of the major health problems that have plagued the human population globally. All dengue virus (DENV) serotypes circulate...
BACKGROUND OBJECTIVES
Dengue and chikungunya infections are one of the major health problems that have plagued the human population globally. All dengue virus (DENV) serotypes circulate within Malaysia with particular serotypes dominating in different years/outbreaks. In the state of Kelantan, an increasing number of DENV and chikungunya virus (CHIKV) new cases have been reported, including several deaths. This study aimed to isolate and detect these arboviruses from adult mosquitoes in Kelantan.
METHODS
Adult mo squito samples were collected from January to August 2019 and were identified according to gender, species and locality. The isolation of the virus was done in C6/36 cells. Dengue NS1 antigen was carried out using direct mosquito lysate and mosquito culture supernatant. Detection and serotyping of the DENV was performed using multiplex RT-PCR and CHIKV detection using a one-step RT-PCR assay.
RESULTS
Of 91 mosquito pools, four were positive for NS1 antigen comprising two pools (2.2%) of male Ae. albopictus (Pulau Melaka and Kubang Siput) and two pools (2.2%) of Ae. aegypti (Kampung Demit Sungai). DENV 1 was detected in one pool (0.9%) of female Ae. albopictus among 114 tested Aedes pools. Two pools of 114 pools (1.7%) from both male Aedes species were positive with double serotypes, DENV 1 and DENV 2 (Pulau Melaka). However, no pool was positive for CHIKV.
INTERPRETATION CONCLUSION
The presence of DENV and the main vectors of arboviruses in Kelantan are pertinent indicators of the need to improve vector controls to reduce arbovirus infections among people in the localities.
Topics: Animals; Malaysia; Dengue Virus; Chikungunya virus; Male; Female; Aedes; Mosquito Vectors; Dengue; Chikungunya Fever; Humans; Viral Nonstructural Proteins; Serogroup
PubMed: 38648407
DOI: 10.4103/0972-9062.392269 -
Journal of Biological Physics Mar 2019In this study, we investigate the binding interactions of two synthetic antiviral peptides (DET2 and DET4) on type II dengue virus (DENV2) envelope protein domain III....
In this study, we investigate the binding interactions of two synthetic antiviral peptides (DET2 and DET4) on type II dengue virus (DENV2) envelope protein domain III. These two antiviral peptides are designed based on the domain III of the DENV2 envelope protein, which has shown significant inhibition activity in previous studies and can be potentially modified further to be active against all dengue strains. Molecular docking was performed using AutoDock Vina and the best-ranked peptide-domain III complex was further explored using molecular dynamics simulations. Molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) was used to calculate the relative binding free energies and to locate the key residues of peptide-protein interactions. The predicted binding affinity correlated well with the previous experimental studies. DET4 outperformed DET2 and is oriented within the binding site through favorable vdW and electrostatic interactions. Pairwise residue decomposition analysis has revealed several key residues that contribute to the binding of these peptides. Residues in DET2 interact relatively lesser with the domain III compared to DET4. Dynamic cross-correlation analysis showed that both the DET2 and DET4 trigger different dynamic patterns on the domain III. Correlated motions were seen between the residue pairs of DET4 and the binding site while binding of DET2 results in anti-correlated motion on the binding site. This work showcases the use of computational study in elucidating and explaining the experiment observation on an atomic level.
Topics: Antiviral Agents; Dengue Virus; Hydrogen Bonding; Molecular Docking Simulation; Peptides; Protein Domains; Protein Structure, Tertiary; Thermodynamics; Viral Envelope Proteins
PubMed: 30680580
DOI: 10.1007/s10867-018-9515-6 -
Blood Jul 2015In this issue of Blood, Simon and colleagues provide the first proof that dengue virus (DENV) raids platelets and steals their translational machinery to replicate and...
In this issue of Blood, Simon and colleagues provide the first proof that dengue virus (DENV) raids platelets and steals their translational machinery to replicate and produce infectious virus.
Topics: Blood Platelets; Dengue; Dengue Virus; Genome, Viral; Humans; Virus Attachment; Virus Replication
PubMed: 26185116
DOI: 10.1182/blood-2015-05-647362 -
Scientific Reports Mar 2017Activated microglial cells are present in dengue virus (DENV)-infected brains; however, the possible effects of DENV on microglia remain unclear. Here, we demonstrated...
Activated microglial cells are present in dengue virus (DENV)-infected brains; however, the possible effects of DENV on microglia remain unclear. Here, we demonstrated DENV caused infection, including viral entry, RNA replication, viral protein expression, and virus release, in the murine microglial cell line BV2. DENV infection caused an increase in the formation of the multipolar phenotype in vitro and in vivo without affecting cell growth and cytotoxicity. DENV infection considerably increased cell motility and disrupting either actin filaments or clathrin retarded such effect. Increase in cell migration was only occurred by DENV infection following a clathrin-regulated endocytosis of DENV entry. Ultraviolet-inactivated DENV did not affect cell migration, and pharmacologically blocking toll-like receptor (TLR) 3 and TLR3-related signaling pathways reduced the DENV-induced increase in cell migration. These results demonstrate an advanced effect of DENV infection on microglial migration via a mechanism involving viral entry, RNA release, and TLR3 signal activation.
Topics: Actin Cytoskeleton; Animals; Cell Line; Cell Movement; Clathrin; Dengue; Dengue Virus; Endocytosis; Humans; Mice; Microglia; Models, Biological; RNA, Viral; Signal Transduction; Toll-Like Receptor 3; Virus Internalization; Virus Replication
PubMed: 28273893
DOI: 10.1038/s41598-017-00182-z -
PLoS Neglected Tropical Diseases Dec 2021Dengue has become a more serious human health concern in China, with increased incidence and expanded outbreak regions. The knowledge of the cross-sectional and...
INTRODUCTION
Dengue has become a more serious human health concern in China, with increased incidence and expanded outbreak regions. The knowledge of the cross-sectional and longitudinal epidemiological characteristics and the evolutionary dynamics of dengue in high-risk areas of China is limited.
METHODS
Records of dengue cases from 2013 to 2016 were obtained from the China Notifiable Disease Surveillance System. Full envelope gene sequences of dengue viruses detected from the high-risk areas of China were collected. Maximum Likelihood tree and haplotype network analyses were conducted to explore the phylogenetic relationship of viruses from high-risk areas of China.
RESULTS
A total of 56,520 cases was reported in China from 2013 to 2016. During this time, Yunnan, Guangdong and Fujian provinces were the high-risk areas. Imported cases occurred almost year-round, and were mainly introduced from Southeast Asia. The first indigenous case usually occurred in June to August, and the last one occurred before December in Yunnan and Fujian provinces but in December in Guangdong Province. Seven genotypes of DENV 1-3 were detected in the high-risk areas, with DENV 1-I the main genotype and DENV 2-Cosmopolitan the secondary one. The Maximum Likelihood trees show that almost all the indigenous viruses separated into different clusters. DENV 1-I viruses were found to be clustered in Guangdong Province, but not in Fujian and Yunnan, from 2013 to 2015. The ancestors of the Guangdong viruses in the cluster in 2013 and 2014 were most closely related to strains from Thailand or Singapore, and the Guangdong virus in 2015 was most closely related to the Guangdong virus of 2014. Based on closest phylogenetic relationships, viruses from Myanmar possibly initiated further indigenous cases in Yunnan, those from Indonesia in Fujian, while viruses from Thailand, Malaysia, Singapore and Indonesia were predominant in Guangdong Province.
CONCLUSIONS
Dengue is still an imported disease in China, although some genotypes continued to circulate in successive years. Viral phylogenies based on the envelope gene suggested periodic introductions of dengue strains into China, primarily from Southeast Asia, with occasional sustained, multi-year transmission in some regions of China.
Topics: China; Cross-Sectional Studies; Dengue; Dengue Virus; Female; Genotype; Humans; Incidence; Male; Phylogeny
PubMed: 34928951
DOI: 10.1371/journal.pntd.0009970 -
International Journal of Medical... 2017Dengue is an important global threat caused by dengue virus (DENV) that records an estimated 390 million infections annually. Despite the availability of CYD-TDV as a... (Review)
Review
Dengue is an important global threat caused by dengue virus (DENV) that records an estimated 390 million infections annually. Despite the availability of CYD-TDV as a commercial vaccine, its long-term efficacy against all four dengue virus serotypes remains unsatisfactory. There is therefore an urgent need for the development of antiviral drugs for the treatment of dengue. Peptide was once a neglected choice of medical treatment but it has lately regained interest from the pharmaceutical industry following pioneering advancements in technology. In this review, the design of peptide drugs, antiviral activities and mechanisms of peptides and peptidomimetics (modified peptides) action against dengue virus are discussed. The development of peptides as inhibitors for viral entry, replication and translation is also described, with a focus on the three main targets, namely, the host cell receptors, viral structural proteins and viral non-structural proteins. The antiviral peptides designed based on these approaches may lead to the discovery of novel anti-DENV therapeutics that can treat dengue patients.
Topics: Antiviral Agents; Dengue; Dengue Vaccines; Dengue Virus; Humans; Peptides; Peptidomimetics; Virus Internalization
PubMed: 29200948
DOI: 10.7150/ijms.21875 -
Viruses Oct 2018Dengue virus (DENV) is estimated to cause 390 million infections per year worldwide. A quarter of these infections manifest clinically and are associated with a...
Dengue virus (DENV) is estimated to cause 390 million infections per year worldwide. A quarter of these infections manifest clinically and are associated with a morbidity and mortality that put a significant burden on the affected regions. Reports of increased frequency, intensity, and extended geographical range of outbreaks highlight the virus's ongoing global spread. Persistent transmission in endemic areas and the emergence in territories formerly devoid of transmission have shaped DENV's current genetic diversity and divergence. This genetic layout is hierarchically organized in serotypes, genotypes, and sub-genotypic clades. While serotypes are well defined, the genotype nomenclature and classification system lack consistency, which complicates a broader analysis of their clinical and epidemiological characteristics. We identify five key challenges: (1) Currently, there is no formal definition of a DENV genotype; (2) Two different nomenclature systems are used in parallel, which causes significant confusion; (3) A standardized classification procedure is lacking so far; (4) No formal definition of sub-genotypic clades is in place; (5) There is no consensus on how to report antigenic diversity. Therefore, we believe that the time is right to re-evaluate DENV genetic diversity in an essential effort to provide harmonization across DENV studies.
Topics: Dengue; Dengue Virus; Genetic Variation; Genotype; Humans; Phylogeny; Terminology as Topic
PubMed: 30340326
DOI: 10.3390/v10100569