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Dengue virus

About: Dengue virus is a research topic. Over the lifetime, 12671 publications have been published within this topic receiving 461406 citations. The topic is also known as: DENV.


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Journal ArticleDOI
TL;DR: The data suggest that the JAK-STAT pathway is part of the A. aegypti mosquito's anti-dengue defense and may act independently of the Toll pathway and the RNAi-mediated antiviral defenses.
Abstract: Here, we show that the major mosquito vector for dengue virus uses the JAK-STAT pathway to control virus infection. Dengue virus infection in Aedes aegypti mosquitoes activates the JAK-STAT immune signaling pathway. The mosquito's susceptibility to dengue virus infection increases when the JAK-STAT pathway is suppressed through RNAi depletion of its receptor Domeless (Dome) and the Janus kinase (Hop), whereas mosquitoes become more resistant to the virus when the negative regulator of the JAK-STAT pathway, PIAS, is silenced. The JAK-STAT pathway exerts its anti-dengue activity presumably through one or several STAT-regulated effectors. We have identified, and partially characterized, two JAK-STAT pathway-regulated and infection-responsive dengue virus restriction factors (DVRFs) that contain putative STAT-binding sites in their promoter regions. Our data suggest that the JAK-STAT pathway is part of the A. aegypti mosquito's anti-dengue defense and may act independently of the Toll pathway and the RNAi-mediated antiviral defenses.

471 citations

Journal ArticleDOI
TL;DR: The results indicate that a symbiotic bacterium can manipulate the host defense system to facilitate its own persistent infection, resulting in a compromise of the mosquito's ability to host human pathogens.
Abstract: Wolbachia are maternally transmitted symbiotic bacteria that can spread within insect populations because of their unique ability to manipulate host reproduction. When introduced to nonnative mosquito hosts, Wolbachia induce resistance to a number of human pathogens, including dengue virus (DENV), Plasmodium, and filarial nematodes, but the molecular mechanism involved is unclear. In this study, we have deciphered how Wolbachia infection affects the Aedes aegypti host in inducing resistance to DENV. The microarray assay indicates that transcripts of genes with functions related to immunity and reduction-oxidation (redox) reactions are up-regulated in Ae. aegypti infected with Wolbachia. Infection with this bacterium leads to induction of oxidative stress and an increased level of reactive oxygen species in its mosquito host. Reactive oxygen species elevation is linked to the activation of the Toll pathway, which is essential in mediating the expression of antioxidants to counterbalance oxidative stress. This immune pathway also is responsible for activation of antimicrobial peptides—defensins and cecropins. We provide evidence that these antimicrobial peptides are involved in inhibition of DENV proliferation in Wolbachia-infected mosquitoes. Utilization of transgenic Ae. aegypti and the RNAi depletion approach has been instrumental in proving the role of defensins and cecropins in the resistance of Wolbachia-infected Ae. aegypti to DENV. These results indicate that a symbiotic bacterium can manipulate the host defense system to facilitate its own persistent infection, resulting in a compromise of the mosquito's ability to host human pathogens. Our discoveries will aid in the development of control strategies for mosquito-transmitted diseases.

461 citations

Journal ArticleDOI
TL;DR: A pair of stochastic simulation models that describe the daily dynamics of dengue virus transmission in the urban environment are developed and compared with reports on the nature of epidemics and seroprevalence of antibody in Honduras in low-lying coastal urbanizations and Tegucigalpa following the initial introduction of d Dengue-1 in 1978 into Central America.
Abstract: We have developed a pair of stochastic simulation models that describe the daily dynamics of dengue virus transmission in the urban environment. Our goal has been to construct comprehensive models that take into account the majority of factors known to influence dengue epidemiology. The models have an orientation toward site-specific data and are designed to be used by operational programs as well as researchers. The first model, the container-inhabiting mosquito simulation model (CIMSiM), a weather-driven dynamic life-table model of container-inhabiting mosquitoes such as Aedes aegypti, provides inputs to the transmission model, the dengue simulation model (DENSiM); a description and validation of the entomology model was published previously. The basis of the transmission model is the simulation of a human population growing in response to country- and age-specific birth and death rates. An accounting of individual serologies is maintained by type of dengue virus, reflecting infection and birth to seropositive mothers. Daily estimates of adult mosquito survival, gonotrophic development, and the weight and number of emerging females from the CIMSiM are used to create the biting mosquito population in the DENSiM. The survival and emergence values determine the size of the population while the rate of gonotrophic development and female weight estimates influence biting frequency. Temperature and titer of virus in the human influences the extrinsic incubation period; titer may also influence the probability of transfer of virus from human to mosquito. The infection model within the DENSiM accounts for the development of virus within individuals and its passage between both populations. As in the case of the CIMSiM, the specific values used for any particular phenomenon are on menus where they can be readily changed. It is possible to simulate concurrent epidemics involving different serotypes. To provide a modicum of validation and to demonstrate the parameterization process for a specific location, we compare simulation results with reports on the nature of epidemics and seroprevalence of antibody in Honduras in low-lying coastal urbanizations and Tegucigalpa following the initial introduction of dengue-1 in 1978 into Central America. We conclude with some additional examples of simulation results to give an indication of the types of questions that can be investigated with the models.

461 citations

Journal ArticleDOI
TL;DR: This study estimated the global economic burden of dengue by country and super-region (groups of epidemiologically similar countries) and contributes to the needs of policy makers, donors, developers, and researchers for economic assessments of d Dengue interventions.
Abstract: Summary Background Dengue is a serious global burden. Unreported and unrecognised apparent dengue virus infections make it difficult to estimate the true extent of dengue and current estimates of the incidence and costs of dengue have substantial uncertainty. Objective, systematic, comparable measures of dengue burden are needed to track health progress, assess the application and financing of emerging preventive and control strategies, and inform health policy. We estimated the global economic burden of dengue by country and super-region (groups of epidemiologically similar countries). Methods We used the latest dengue incidence estimates from the Institute for Health Metrics and Evaluation's Global Burden of Disease Study 2013 and several other data sources to assess the economic burden of symptomatic dengue cases in the 141 countries and territories with active dengue transmission. From the scientific literature and regressions, we estimated cases and costs by setting, including the non-medical setting, for all countries and territories. Findings Our global estimates suggest that in 2013 there were a total of 58·40 million symptomatic dengue virus infections (95% uncertainty interval [95% UI] 24 million–122 million), including 13 586 fatal cases (95% UI 4200–34 700), and that the total annual global cost of dengue illness was US$8·9 billion (95% UI 3·7 billion–19·7 billion). The global distribution of dengue cases is 18% admitted to hospital, 48% ambulatory, and 34% non-medical. Interpretation The global cost of dengue is substantial and, if control strategies could reduce dengue appreciably, billions of dollars could be saved globally. In estimating dengue costs by country and setting, this study contributes to the needs of policy makers, donors, developers, and researchers for economic assessments of dengue interventions, particularly with the licensure of the first dengue vaccine and promising developments in other technologies. Funding Sanofi Pasteur.

459 citations

Journal ArticleDOI
TL;DR: The first time that monospecific antibodies have been available for all of these unique antigenic determinants was reported in this article, where the Hybridoma cell lines producing dengue type-specific antibodies were deposited in the American Type Culture Collection (Type Culture Collection) for general distribution.
Abstract: Monoclonal antibodies produced against the four dengue virus serotypes identified four categories of reactions by immunofluorescence: flavivirus group reactive, dengue complex specific, dengue subcomplex specific (DEN-1, DEN-3), and dengue serotype specific. This is the first time that monospecific antibodies have been available for all of these unique antigenic determinants. Hybridoma cell lines producing dengue type-specific antibodies have been deposited in the Hybridoma Cell Bank of the American Type Culture Collection (Rockville, MD) for general distribution.

456 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023546
20221,066
2021780
2020912
2019849
2018930