-
Human Vaccines & Immunotherapeutics 2014Dengue is a major threat for public health in tropical and subtropical countries around the world. In the absence of a licensed vaccine and effective antiviral... (Review)
Review
Dengue is a major threat for public health in tropical and subtropical countries around the world. In the absence of a licensed vaccine and effective antiviral therapies, control measures have been based on education activities and vector elimination. Current efforts for developing a vaccine are both promising and troubling. At the advent of the introduction of a tetravalent dengue vaccine, molecular surveillance of the circulating genotypes in different geographical regions has gained considerable importance. A growing body of in vitro, preclinical, and clinical phase studies suggest that vaccine conferred protection in a geographical area could depends on the coincidence of the dengue virus genotypes included in the vaccine and those circulating. In this review we present the state-of-the-art in this field, highlighting the need of deeper knowledge on neutralizing immune response for making decisions about future vaccine approval and the potential need for different vaccine composition for regional administration.
Topics: Dengue; Dengue Vaccines; Dengue Virus; Drug Approval; Epidemiological Monitoring; Genotype; Humans; Molecular Epidemiology
PubMed: 25483495
DOI: 10.4161/hv.29563 -
Viruses Jul 2021Dengue virus (DENV) is one of the most prevalent neglected tropical diseases, with half of the world's population at risk of infection. In Nepal, DENV was first reported...
Dengue virus (DENV) is one of the most prevalent neglected tropical diseases, with half of the world's population at risk of infection. In Nepal, DENV was first reported in 2004, and its prevalence is increasing every year. The present study aimed to obtain and characterize the full-length genome sequence of DENV from the 2017 outbreak. Hospital-based surveillance was conducted in two provinces of Nepal during the outbreak. Acute-phase serum samples were collected from 141 clinically suspected dengue patients after the rainy season. By serological and molecular techniques, 37 (26.9%) and 49 (34.8%), respectively, were confirmed as dengue patients. The cosmopolitan genotype of DENV-2 was isolated from 27 laboratory-confirmed dengue patients. Genomic analysis showed many amino acid substitutions distributed mainly among the E, NS3, and NS5 genes. Phylogenetic analyses of the whole genome sequence revealed two clades (Asian and Indian) among DENV-2 isolates from Nepal. The DENV isolates from hilly and Terai areas were similar to Asian and Indian strains, respectively. Further genomic study on different DENV serotypes is warranted to understand DENV epidemics in Nepal, where there are limited scientific resources and infrastructure.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Cross-Sectional Studies; Dengue; Dengue Virus; Disease Outbreaks; Female; Genotype; Humans; Infant; Male; Middle Aged; Nepal; Phylogeny; Serogroup; Whole Genome Sequencing; Young Adult
PubMed: 34452310
DOI: 10.3390/v13081444 -
The American Journal of Tropical... Oct 2019The incidence of dengue is increasing in Guangdong, China, with the largest outbreak to date in 2014. Widespread awareness of epidemiological and molecular...
The incidence of dengue is increasing in Guangdong, China, with the largest outbreak to date in 2014. Widespread awareness of epidemiological and molecular characteristics of the dengue virus (DENV) is required. In 2014, we isolated the virus from patients and sequenced its genome. The sequences of DENV isolated from Guangdong and other countries screened since 2005 were studied to establish molecular evolutionary databases along with epidemiological data to explore its epidemiological, phylogenetic, and molecular characteristics. Causes underlying the occurrence of the dengue epidemic included importation and localization of the virus. The number of indigenous cases significantly exceeded that of imported cases. Dengue virus 1 is the most important serotype and caused the long-term epidemic locally. Based on the data available since 2005, DENV1 was divided into three genotypes (I, IV, and V). Only genotypes I and V were detected in 2014. In 2014, an epidemic involving old lineages of DENV1 genotype V occurred after 2 years of silence. The genotype was previously detected from 2009 to 2011. Genotype I, which caused recent epidemics, demonstrated a continuation of new lineages, and a predictive pattern of molecular evolution since 2005 among the four lineages was present. The DENV isolated from Guangdong was closely related to those causing large-scale epidemics in neighboring countries, suggesting the possibility of its import from these countries. The lack of sufficient epidemiological data and evidence on the local mosquito-borne DENV emphasizes the importance of studying the molecular evolutionary features and establishing a well-established phylogenetic tree for dengue prevention and control in Guangdong.
Topics: Dengue Virus; Endoplasmic Reticulum Chaperone BiP; Evolution, Molecular; Genotype; Heat-Shock Proteins; Molecular Docking Simulation; Phylogeny; Protein Conformation; Viral Proteins
PubMed: 31392945
DOI: 10.4269/ajtmh.18-0951 -
PloS One 2013Dengue virus is the most prevalent mosquito-borne virus worldwide. In this study, we used pyrosequencing to analyze the whole viral genome of two mouse-adapted strains,...
Dengue virus is the most prevalent mosquito-borne virus worldwide. In this study, we used pyrosequencing to analyze the whole viral genome of two mouse-adapted strains, D2S10 and D2S20, that induce a dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS)-like lethal disease in mice lacking the type I and/or type II interferon receptors. Previous experiments with D2S10 indicated that N124D and K128E mutations in the envelope protein were responsible for the severe disease induced in mice compared to its parental strain PL046. Here we demonstrate that D2S20 is more virulent than D2S10 and captured the presence of five key amino acid mutations--T70I, N83D, and K122I in envelope (E), and A62T in nonstructural protein 2A (NS2A) and G605V in nonstructural protein 5 (NS5)--that may account for this. These findings set the foundation for further dissection of the viral determinants responsible for dengue disease manifestations in mouse models.
Topics: Animals; Biological Evolution; Dengue; Dengue Virus; Mice; Mutation
PubMed: 23342105
DOI: 10.1371/journal.pone.0054220 -
Journal of Virology May 2014During dengue virus infection of host cells, intracellular membranes are rearranged into distinct subcellular structures such as double-membrane vesicles, convoluted...
UNLABELLED
During dengue virus infection of host cells, intracellular membranes are rearranged into distinct subcellular structures such as double-membrane vesicles, convoluted membranes, and tubular structures. Recent electron tomographic studies have provided a detailed three-dimensional architecture of the double-membrane vesicles, representing the sites of dengue virus replication, but temporal and spatial evidence linking membrane morphogenesis with viral RNA synthesis is lacking. Integrating techniques in electron tomography and molecular virology, we defined an early period in virus-infected mosquito cells during which the formation of a virus-modified membrane structure, the double-membrane vesicle, is proportional to the rate of viral RNA synthesis. Convoluted membranes were absent in dengue virus-infected C6/36 cells. Electron tomographic reconstructions elucidated a high-resolution view of the replication complexes inside vesicles and allowed us to identify distinct pathways of particle formation. Hence, our findings extend the structural details of dengue virus replication within mosquito cells and highlight their differences from mammalian cells.
IMPORTANCE
Dengue virus induces several distinct intracellular membrane structures within the endoplasmic reticulum of mammalian cells. These structures, including double-membrane vesicles and convoluted membranes, are linked, respectively, with viral replication and viral protein processing. However, dengue virus cycles between two disparate animal groups with differing physiologies: mammals and mosquitoes. Using techniques in electron microscopy, we examined the differences between intracellular structures induced by dengue virus in mosquito cells. Additionally, we utilized techniques in molecular virology to temporally link events in virus replication to the formation of these dengue virus-induced membrane structures.
Topics: Animals; Cell Line; Culicidae; Dengue Virus; Electron Microscope Tomography; Imaging, Three-Dimensional; Intracellular Membranes; Virus Replication
PubMed: 24522909
DOI: 10.1128/JVI.00118-14 -
Journal of Virology Dec 2005Dengue virus type 4 (DENV-4) was first reported in the Americas in 1981, where it caused epidemics of dengue fever throughout the region. In the same year, the region's...
Dengue virus type 4 (DENV-4) was first reported in the Americas in 1981, where it caused epidemics of dengue fever throughout the region. In the same year, the region's first epidemic of dengue hemorrhagic fever was reported, caused by an Asian strain of dengue virus type 2 (DENV-2) that was distinct from the American subtype circulating previously. Despite the importance of these epidemics, little is known about the rates or determinants of viral spread among island and mainland populations or their directions of movement. We employed a Bayesian coalescent approach to investigate the transmission histories of DENV-2 and DENV-4 since their introduction in 1981 and a parsimony method to assess patterns of strain migration. For both viruses there was an initial invasion phase characterized by an exponential increase in the number of DENV lineages, after which levels of genetic diversity remained constant despite reported fluctuations in DENV-2 and DENV-4 activity. Strikingly, viral lineage numbers increased far more rapidly for DENV-4 than DENV-2, indicative of a more rapid rate of exponential population growth in DENV-4 or a higher rate of geographic dispersal, allowing this virus to move more effectively among localities. We propose that these contrasting dynamics may reflect underlying differences in patterns of host immunity. Despite continued gene flow along particular transmission routes, the overall extent of viral traffic was less than expected under panmixis. Hence, DENV in the Americas has a clear geographic structure that maintains viral diversity between outbreaks.
Topics: Americas; Base Sequence; DNA, Viral; Dengue; Dengue Virus; Disease Outbreaks; Humans; Molecular Epidemiology; Phylogeny; Serotyping
PubMed: 16282468
DOI: 10.1128/JVI.79.23.14680-14687.2005 -
Current Opinion in Virology Oct 2016If a freshly minted genome contains a mutation that confers drug resistance, will it be selected in the presence of the drug? Not necessarily. During viral infections,... (Review)
Review
If a freshly minted genome contains a mutation that confers drug resistance, will it be selected in the presence of the drug? Not necessarily. During viral infections, newly synthesized viral genomes occupy the same cells as parent and other progeny genomes. If the antiviral target is chosen so that the drug-resistant progeny's growth is dominantly inhibited by the drug-susceptible members of its intracellular family, its outgrowth can be suppressed. Precedent for 'dominant drug targeting' as a deliberate approach to suppress the outgrowth of inhibitor-resistant viruses has been established for envelope variants of vesicular stomatitis virus and for capsid variants of poliovirus and dengue virus. Small molecules that stabilize oligomeric assemblages are a promising means to an unfit family to destroy the effectiveness of a newborn drug-resistant relative due to the co-assembly of drug-susceptible and drug-resistant monomers.
Topics: Antiviral Agents; Dengue Virus; Drug Resistance, Viral; Genetics, Population; Humans; Poliovirus; Selection, Genetic; Vesiculovirus; Virus Replication
PubMed: 27764731
DOI: 10.1016/j.coviro.2016.09.011 -
TheScientificWorldJournal 2013An increased number of dengue cases with neurological complications have been reported in recent years. The lack of reliable animal models for dengue has hindered...
An increased number of dengue cases with neurological complications have been reported in recent years. The lack of reliable animal models for dengue has hindered studies on dengue virus (DENV) pathogenesis and cellular tropism in vivo. We further investigate the tropism of DENV for the human central nervous system (CNS), characterizing DENV interactions with cell surface proteins in human CNS cells by virus overlay protein binding assays (VOPBA) and coimmunoprecipitations. In VOPBA, three membrane proteins (60, 70, and 130 kDa) from the gray matter bound the entire virus particle, whereas only a 70 kDa protein bound in white matter. The coimmunoprecipitation assays revealed three proteins from gray matter consistently binding virus particles, one clearly distinguishable protein (~32 kDa) and two less apparent proteins (100 and 130 kDa). Monoclonal anti-NS3 targeted the virus protein in primary cell cultures of human CNS treated with DENV-2, which also stained positive for NeuH, a neuron-specific marker. Thus, our results indicate (1) that DENV-2 exhibited a direct tropism for human neurons and (2) that human neurons sustain an active DENV replication as was demonstrated by the presence of the NS3 viral antigen in primary cultures of these cells treated with DENV-2.
Topics: Adolescent; Brain; Child; Dengue Virus; Electrophoresis, Polyacrylamide Gel; Female; Humans; Immunoprecipitation; In Vitro Techniques; Male; Protein Binding; Viral Proteins; Virus Replication
PubMed: 24302878
DOI: 10.1155/2013/904067 -
Virology Jul 2007This study demonstrated that the lambda- and iota-carrageenans, sulfated polysaccharides containing linear chains of galactopyranosyl residues, are potent inhibitors of...
This study demonstrated that the lambda- and iota-carrageenans, sulfated polysaccharides containing linear chains of galactopyranosyl residues, are potent inhibitors of dengue virus type 2 (DENV-2) and 3 (DENV-3) multiplication in Vero and HepG2 cells, with values of effective concentration 50% from 0.14 to 4.1 microg/ml. This activity was assayed by plaque reduction, virus yield inhibition and antigen expression tests, and was independent of the input multiplicity of infection in the range 0.001-1. The inhibitory action of the lambda-carrageenan, an heparan sulfate (HS)-imitative compound, was exerted by a dual interference with virus adsorption and internalization of nucleocapsid into the cytoplasm. Although virus particles may enter the cell when compound was added after DENV-2 adsorption, as shown by intracellular uptake of radiolabeled DENV-2 particles and quantitative RT-PCR, infectious center and virion uncoating assays have shown that carrageenan-treated virions cannot be released from the endosomes. Viral protein synthesis, the first step of macromolecular synthesis after DENV entry to the host cell, was not affected by the carrageenan. Furthermore, no inhibition of virus multiplication was detected when the entry process was bypassed through DENV-2 RNA transfection into the cell. The dual sites of action of an HS-like molecule suggest that, at least in monkey kidney and human hepatic cells, the HS residues in the cell membrane appear to act as mediators for DENV-2 entry, an interesting alternative target for flavivirus therapy.
Topics: Animals; Carrageenan; Cell Line; Dengue; Dengue Virus; Dose-Response Relationship, Drug; Humans; Virus Replication
PubMed: 17337028
DOI: 10.1016/j.virol.2007.01.043 -
PLoS Neglected Tropical Diseases Feb 2016Dengue has emerged as one of the most important infectious diseases in the last five decades. Evidence indicates the expansion of dengue virus endemic areas and...
BACKGROUND
Dengue has emerged as one of the most important infectious diseases in the last five decades. Evidence indicates the expansion of dengue virus endemic areas and consequently the exponential increase of dengue virus infections across the subtropics. The clinical manifestations of dengue virus infection include sudden fever, rash, headache, myalgia and in more serious cases, spontaneous bleeding. These manifestations occur in children as well as in adults. Defining the epidemiology of dengue in a given area is critical to understanding the disease and devising effective public health strategies.
METHODOLOGY/PRINCIPAL FINDINGS
Here, we report the results from a prospective cohort study of 4380 adults in West Java, Indonesia, from 2000-2004 and 2006-2009. A total of 2167 febrile episodes were documented and dengue virus infections were confirmed by RT-PCR or serology in 268 cases (12.4%). The proportion ranged from 7.6 to 41.8% each year. The overall incidence rate of symptomatic dengue virus infections was 17.3 cases/1,000 person years and between September 2006 and April 2008 asymptomatic infections were 2.6 times more frequent than symptomatic infections. According to the 1997 WHO classification guidelines, there were 210 dengue fever cases, 53 dengue hemorrhagic fever cases (including one dengue shock syndrome case) and five unclassified cases. Evidence for sequential dengue virus infections was seen in six subjects. All four dengue virus serotypes circulated most years. Inapparent dengue virus infections were predominantly associated with DENV-4 infections.
CONCLUSIONS/SIGNIFICANCE
Dengue virus was responsible for a significant percentage of febrile illnesses in an adult population in West Java, Indonesia, and this percentage varied from year to year. The observed incidence rate during the study period was 43 times higher than the reported national or provincial rates during the same time period. A wide range of clinical severity was observed with most infections resulting in asymptomatic disease. The circulation of all four serotypes of dengue virus was observed in most years of the study.
Topics: Adolescent; Adult; Aged; Dengue; Dengue Virus; Female; Humans; Incidence; Indonesia; Male; Middle Aged; Molecular Sequence Data; Prospective Studies; RNA, Viral; Reverse Transcriptase Polymerase Chain Reaction; Sequence Analysis, DNA; Young Adult
PubMed: 26872216
DOI: 10.1371/journal.pntd.0004390