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PLoS Neglected Tropical Diseases 2014A literature survey and analysis was conducted to describe the epidemiology of dengue disease in Malaysia between 2000 and 2012. Published literature was searched for... (Review)
Review
UNLABELLED
A literature survey and analysis was conducted to describe the epidemiology of dengue disease in Malaysia between 2000 and 2012. Published literature was searched for epidemiological studies of dengue disease, using specific search strategies for each electronic database; 237 relevant data sources were identified, 28 of which fulfilled the inclusion criteria. The epidemiology of dengue disease in Malaysia was characterized by a non-linear increase in the number of reported cases from 7,103 in 2000 to 46,171 in 2010, and a shift in the age range predominance from children toward adults. The overall increase in dengue disease was accompanied by a rise in the number, but not the proportion, of severe cases. The dominant circulating dengue virus serotypes changed continually over the decade and differed between states. Several gaps in epidemiological knowledge were identified; in particular, studies of regional differences, age-stratified seroprevalence, and hospital admissions.
PROTOCOL REGISTRATION
PROSPERO #CRD42012002293.
Topics: Age Distribution; Dengue; Dengue Virus; Humans; Malaysia; Seasons; Seroepidemiologic Studies; Serogroup; Sex Distribution; Socioeconomic Factors
PubMed: 25375211
DOI: 10.1371/journal.pntd.0003159 -
Annual Review of Virology Sep 2018Dengue virus (DENV) is the most prevalent medically important mosquito-borne virus in the world. Upon DENV infection of a host cell, DENV nonstructural protein 1 (NS1)... (Review)
Review
Dengue virus (DENV) is the most prevalent medically important mosquito-borne virus in the world. Upon DENV infection of a host cell, DENV nonstructural protein 1 (NS1) can be found intracellularly as a monomer, associated with the cell surface as a dimer, and secreted as a hexamer into the bloodstream. NS1 plays a variety of roles in the viral life cycle, particularly in RNA replication and immune evasion of the complement pathway. Over the past several years, key roles for NS1 in the pathogenesis of severe dengue disease have emerged, including direct action of the protein on the vascular endothelium and triggering release of vasoactive cytokines from immune cells, both of which result in endothelial hyperpermeability and vascular leak. Importantly, the adaptive immune response generates a robust response against NS1, and its potential contribution to dengue vaccines is also discussed.
Topics: Cytokines; Dengue; Dengue Vaccines; Dengue Virus; Endothelium, Vascular; Host-Pathogen Interactions; Immune Evasion; Permeability; RNA, Viral; Viral Nonstructural Proteins; Virus Replication
PubMed: 30044715
DOI: 10.1146/annurev-virology-101416-041848 -
PloS One 2021Dengue is an endemic disease in Colombia. Norte de Santander is a region on the border of Colombia and Venezuela and has reported the co-circulation and simultaneous...
Dengue is an endemic disease in Colombia. Norte de Santander is a region on the border of Colombia and Venezuela and has reported the co-circulation and simultaneous co-infection of different serotypes of the dengue virus (DENV). This study aimed to conduct a phylogenetic analysis on the origin and genetic diversity of DENV strains circulating in this bordering region. Serum samples were collected from patients who were clinically diagnosed with febrile syndrome associated with dengue during two periods. These samples were tested for DENV and serotyping was performed using reverse transcriptase-polymerase chain reaction. Subsequently, positive samples were amplified and the envelope protein gene of DENV was sequenced. Phylogenetic and phylogeographic analyses were performed using the sequences obtained. Basic local alignment search tool analysis confirmed that six and eight sequences belonged to DENV-1 and DENV-2, respectively. The phylogenetic analysis of DENV-1 showed that the sequences belonged to genotype V and clade I; they formed two groups: in the first group, two sequences showed a close phylogenetic relationship with strains from Ecuador and Panama, whereas the other four sequences were grouped with strains from Venezuela and Colombia. In the case of DENV-2, the analysis revealed that the sequences belonged to the Asian-American genotype and clade III. Furthermore, they formed two groups; in the first group, three sequences were grouped with strains from Colombia and Venezuela, whereas the other five were grouped with strains from Venezuela, Colombia and Honduras. This phylogenetic analysis suggests that the geographical proximity between Colombia and Venezuela is favourable for the export and import of different strains among serotypes or clades of the same DENV serotype, which could favour the spread of new outbreaks caused by new strains or genetic variants of this arbovirus. Therefore, this information highlights the importance of monitoring the transmission of DENV at border regions.
Topics: Adolescent; Adult; Child; Colombia; Dengue; Dengue Virus; Evolution, Molecular; Female; Genotype; Humans; Male; Phylogeny; Phylogeography; Reverse Transcriptase Polymerase Chain Reaction; Sequence Analysis, DNA; Serogroup; Venezuela; Young Adult
PubMed: 34048474
DOI: 10.1371/journal.pone.0252379 -
Scientific Reports Jun 2017The recent development of a nanopore-type portable DNA sequencer has changed the way we think about DNA sequencing. We can perform sequencing directly in the field,...
The recent development of a nanopore-type portable DNA sequencer has changed the way we think about DNA sequencing. We can perform sequencing directly in the field, where we collect the samples. Here, we report the development of a novel method to detect and genotype tropical disease pathogens, using dengue fever as a model. By combining the sequencer with isothermal amplification that only requires a water bath, we were able to amplify and sequence target viral genomes with ease. Starting from a serum sample, the entire procedure could be finished in a single day. The analysis of blood samples collected from 141 Indonesian patients demonstrated that this method enables the clinical identification and serotyping of the dengue virus with high sensitivity and specificity. The overall successful detection rate was 79%, and a total of 58 SNVs were detected. Similar analyses were conducted on 80 Vietnamese and 12 Thai samples with similar performance. Based on the obtained sequence information, we demonstrated that this approach is able to produce indispensable information for etiologically analyzing annual or regional diversifications of the pathogens.
Topics: Dengue; Dengue Virus; Genotype; Genotyping Techniques; Humans; Nucleic Acid Amplification Techniques; Sensitivity and Specificity; Sequence Analysis, DNA; Serotyping
PubMed: 28615658
DOI: 10.1038/s41598-017-03734-5 -
Antimicrobial Agents and Chemotherapy Feb 2015Dengue fever is a severe, widespread, and neglected disease with more than 2 million diagnosed infections per year. The dengue virus NS2B/NS3 protease (PR) represents a...
Dengue fever is a severe, widespread, and neglected disease with more than 2 million diagnosed infections per year. The dengue virus NS2B/NS3 protease (PR) represents a prime target for rational drug design. At the moment, there are no clinical PR inhibitors (PIs) available. We have identified diaryl (thio)ethers as candidates for a novel class of PIs. Here, we report the selective and noncompetitive inhibition of the serotype 2 and 3 dengue virus PR in vitro and in cells by benzothiazole derivatives exhibiting 50% inhibitory concentrations (IC50s) in the low-micromolar range. Inhibition of replication of DENV serotypes 1 to 3 was specific, since all substances influenced neither hepatitis C virus (HCV) nor HIV-1 replication. Molecular docking suggests binding at a specific allosteric binding site. In addition to the in vitro assays, a cell-based PR assay was developed to test these substances in a replication-independent way. The new compounds inhibited the DENV PR with IC50s in the low-micromolar or submicromolar range in cells. Furthermore, these novel PIs inhibit viral replication at submicromolar concentrations.
Topics: Antiviral Agents; Cell Line; Dengue Virus; HIV-1; Humans; Molecular Docking Simulation; Protease Inhibitors; Serine Endopeptidases; Viral Nonstructural Proteins; Virus Replication
PubMed: 25487800
DOI: 10.1128/AAC.03543-14 -
Epidemiology and Infection Mar 2017We studied the evolution, genotypes, and the molecular clock of dengue virus serotype 1 (DENV-1), between 2001 and 2014 in Guangzhou, China. The analysis of the envelope...
We studied the evolution, genotypes, and the molecular clock of dengue virus serotype 1 (DENV-1), between 2001 and 2014 in Guangzhou, China. The analysis of the envelope (E) gene sequences of 67 DENV-1 strains isolated in Guangzhou, together with 58 representative sequences downloaded from NCBI, have shown shifts in viral genotypes. The genotype changed several times, from genotype I to IV in 2002, from IV to I in 2005, and from I to V in 2014. These genotype shifts may be the cause of DENV outbreaks. The diversity of genotypes and clades demonstrates a high risk of future outbreaks in Guangzhou. The mean rate of virus nucleotide substitution in Guangzhou was determined to be 7·77 × 10-4 per site per year, which represents a medium substitution rate compared to two other countries. Our research can point to different ancestors of the isolated strains, which may further reveal the different origins and transmission of DENV-1 strains in Guangzhou.
Topics: China; Dengue; Dengue Virus; Disease Outbreaks; Evolution, Molecular; Gene Products, env; Genetic Variation; Genotype; Humans; Molecular Epidemiology; Sequence Analysis, DNA
PubMed: 27919298
DOI: 10.1017/S0950268816002429 -
PLoS Pathogens Mar 2021Dengue virus (DENV) causes dengue fever and severe hemorrhagic fever in humans and is primarily transmitted by Aedes aegypti and A. albopictus mosquitoes. The incidence...
Dengue virus (DENV) causes dengue fever and severe hemorrhagic fever in humans and is primarily transmitted by Aedes aegypti and A. albopictus mosquitoes. The incidence of DENV infection has been gradually increasing in recent years due to global urbanization and international travel. Understanding the virulence determinants in host and vector transmissibility of emerging epidemic DENV will be critical to combat potential outbreaks. The DENV serotype 2 (DENV-2), which caused a widespread outbreak in Taiwan in 2015 (TW2015), is of the Cosmopolitan genotype and is phylogenetically related to the virus strain linked to another large outbreak in Indonesia in 2015. We found that the TW2015 virus was highly virulent in type I and type II interferon-deficient mice, with robust replication in spleen, lung, and intestine. The TW2015 virus also had high transmissibility to Aedes mosquitoes and could be effectively spread in a continuous mosquitoes-mouse-mosquitoes-mouse transmission cycle. By making 16681-based mutants carrying different segments of the TW2015 virus, we identified the structural pre-membrane (prM) and envelope (E) genes as key virulence determinants in the host, with involvement in the high transmissibility of the TW2015 virus in mosquitoes. The transmission mouse model will make a useful platform for evaluation of DENV with high epidemic potential and development of new strategies against dengue outbreaks.
Topics: Animals; Culicidae; Dengue; Dengue Virus; Disease Models, Animal; Genotype; Insect Vectors; Mice; Virulence
PubMed: 33784371
DOI: 10.1371/journal.ppat.1009480 -
MSphere Apr 2020The incidence of locally acquired dengue infections increased during the last decade in the United States, compelling a sustained research effort concerning the dengue...
The incidence of locally acquired dengue infections increased during the last decade in the United States, compelling a sustained research effort concerning the dengue mosquito vector, , and its microbiome, which has been shown to influence virus transmission success. We examined the "metavirome" of four populations of mosquitoes collected in 2016 to 2017 in Manatee County, FL. Unexpectedly, we discovered that dengue virus serotype 4 (DENV4) was circulating in these mosquito populations, representing the first documented case of such a phenomenon in the absence of a local DENV4 human case in this county over a 2-year period. We confirmed that all of the mosquito populations carried the same DENV4 strain, assembled its full genome, validated infection orthogonally by reverse transcriptase PCR, traced the virus origin, estimated the time period of its introduction to the Caribbean region, and explored the viral genetic signatures and mosquito-specific virome associations that potentially mediated DENV4 persistence in mosquitoes. We discuss the significance of prolonged maintenance of the DENV4 infections in that occurred in the absence of a DENV4 human index case in Manatee County with respect to the inability of current surveillance paradigms to detect mosquito vector infections prior to a potential local outbreak. Since 1999, dengue outbreaks in the continental United States involving local transmission have occurred only episodically and only in Florida and Texas. In Florida, these episodes appear to be coincident with increased introductions of dengue virus into the region through human travel and migration from countries where the disease is endemic. To date, the U.S. public health response to dengue outbreaks has been largely reactive, and implementation of comprehensive arbovirus surveillance in advance of predictable transmission seasons, which would enable proactive preventative efforts, remains unsupported. The significance of our finding is that it is the first documented report of DENV4 transmission to and maintenance within a local mosquito vector population in the continental United States in the absence of a human case during two consecutive years. Our data suggest that molecular surveillance of mosquito populations in high-risk, high-tourism areas of the United States may enable proactive, targeted vector control before potential arbovirus outbreaks.
Topics: Aedes; Animals; Dengue Virus; Disease Outbreaks; Female; Florida; Genome, Viral; Mosquito Vectors; Seasons; Serogroup; Virome
PubMed: 32350095
DOI: 10.1128/mSphere.00316-20 -
Frontiers in Cellular and Infection... 2018In 2015, a dengue outbreak with 1,067 reported cases occurred in Xishuangbanna, a city in China that borders Burma and Laos. To characterize the virus, the complete...
In 2015, a dengue outbreak with 1,067 reported cases occurred in Xishuangbanna, a city in China that borders Burma and Laos. To characterize the virus, the complete genome sequence was obtained and phylogenetic, mutation, substitution and recombinant analyses were performed. DENV-NS1 positive serum samples were collected from dengue fever patients, and complete genome sequences were obtained through RT-qPCR from these serum samples. Phylogenetic trees were then constructed by maximum likelihood phylogeny test (MEGA7.0), followed by analysis of nucleotide mutation and amino acid substitution. The recombination events among DENVs were also analyzed by RDP4 package. The diversity analysis of secondary structure for translated viral proteins was also performed. The complete genome sequences of four amplified viruses (YNXJ10, YNXJ12, YNXJ13, and YNXJ16) were 10,742, 10,742, 10,741, and 10,734 nucleotides in length, and phylogenetic analysis classified the viruses as cosmopolitan genotype of DENV-2. All viruses were close to DENV Singapore 2013 (KX380828.1) and the DENV China 2013 (KF479233.1). In comparison to DENV-2SS (M29095), the total numbers of base substitutions were 712 nt (YNXJ10), 809 nt (YNXJ12), 772 nt (YNXJ13), and 841 nt (YNXJ16), resulting in 109, 171, 130, and 180 amino acid substitutions in translated regions, respectively. In addition, compared with KX380828.1, there were 44, 105, 64, and 116 amino acid substitutions in translated regions, respectively. The highest mutation rate occurred in the prM region, and the lowest mutation rate occurred in the NS4B region. Most of the recombination events occurred in the prM, E and NS2B/3 regions, which corresponded with the mutation frequency of the related portion. Secondary structure prediction within the 3,391 amino acids of DENV structural proteins showed there were 7 new possible nucleotide-binding sites and 6 lost sites compared to DENV-2SS. In addition, 41 distinct amino acid changes were found in the helix regions, although the distribution of the exposed and buried regions changed only slightly. Our findings may help to understand the intrinsic geographical relatedness of DENV-2 and contributes to the understanding of viral evolution and its impact on the epidemic potential and pathogenicity of DENV.
Topics: Amino Acid Substitution; China; Cluster Analysis; Dengue; Dengue Virus; Disease Outbreaks; Genetic Variation; Genotype; Humans; Molecular Epidemiology; Mutation; Phylogeny; Real-Time Polymerase Chain Reaction; Recombination, Genetic; Reverse Transcriptase Polymerase Chain Reaction; Sequence Homology; Serogroup; Whole Genome Sequencing
PubMed: 29998087
DOI: 10.3389/fcimb.2018.00219 -
Journal of Applied Microbiology Oct 2015To identify a novel antiviral peptide against dengue virus serotype 2 (DENV-2) by screening a phage display peptide library and to evaluate its in vitro antiviral...
AIM
To identify a novel antiviral peptide against dengue virus serotype 2 (DENV-2) by screening a phage display peptide library and to evaluate its in vitro antiviral activity and mode of action.
METHODS AND RESULTS
A phage display peptide library was biopanned against purified DENV-2 and resulted in the identification and selection of a peptide (peptide gg-ww) for further investigation. ELISA was performed, and peptide gg-ww was shown to possess the highest binding affinity against DENV-2. Thus, peptide gg-ww was synthesized for cytotoxicity and antiviral assays. Virus plaque reduction assay, real-time PCR and immunofluorescence assay were used to investigate the inhibitory effect of peptide gg-ww on DENV-2 infection in Vero cells. Three different assays (pre-, simultaneous and post-treatments assays) were performed to investigate the peptide's mode of action. Results indicated that peptide gg-ww possessed strong antiviral activity with a ~96% inhibition rate, which was achieved at 250 μmol l(-1) . Viral replication was inhibited during a simultaneous treatment assay, indicating that the entry of the virus was impeded by this peptide.
CONCLUSIONS
Peptide gg-ww displayed antiviral action against DENV-2 by targeting an early stage of viral replication (i.e. during viral entry).
SIGNIFICANCE AND IMPACT OF THE STUDY
Peptide gg-ww may represent a new therapeutic candidate for the treatment of DENV infections and is a potential candidate to be developed as a peptide drug.
Topics: Animals; Antiviral Agents; Chlorocebus aethiops; Dengue; Dengue Virus; Humans; Molecular Sequence Data; Peptides; Serogroup; Vero Cells; Viral Plaque Assay; Virus Replication
PubMed: 26248692
DOI: 10.1111/jam.12921