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      Complex Modulation of the Aedes aegypti Transcriptome in Response to Dengue Virus Infection

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          Abstract

          Dengue fever is the most important arboviral disease world-wide, with Aedes aegypti being the major vector. Interactions between the mosquito host and dengue viruses (DENV) are complex and vector competence varies among geographically-distinct Ae. aegypti populations. Additionally, dengue is caused by four antigenically-distinct viral serotypes (DENV1–4), each with multiple genotypes. Each virus genotype interacts differently with vertebrate and invertebrate hosts. Analyses of alterations in mosquito transcriptional profiles during DENV infection are expected to provide the basis for identifying networks of genes involved in responses to viruses and contribute to the molecular-genetic understanding of vector competence. In addition, this knowledge is anticipated to support the development of novel disease-control strategies. RNA-seq technology was used to assess genome-wide changes in transcript abundance at 1, 4 and 14 days following DENV2 infection in carcasses, midguts and salivary glands of the Ae. aegypti Chetumal strain. DENV2 affected the expression of 397 Ae. aegypti genes, most of which were down-regulated by viral infection. Differential accumulation of transcripts was mainly tissue- and time-specific. Comparisons of our data with other published reports reveal conservation of functional classes, but limited concordance of specific mosquito genes responsive to DENV2 infection. These results indicate the necessity of additional studies of mosquito-DENV interactions, specifically those focused on recently-derived mosquito strains with multiple dengue virus serotypes and genotypes.

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          Most cited references47

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          Impact of daily temperature fluctuations on dengue virus transmission by Aedes aegypti.

          Most studies on the ability of insect populations to transmit pathogens consider only constant temperatures and do not account for realistic daily temperature fluctuations that can impact vector-pathogen interactions. Here, we show that diurnal temperature range (DTR) affects two important parameters underlying dengue virus (DENV) transmission by Aedes aegypti. In two independent experiments using different DENV serotypes, mosquitoes were less susceptible to virus infection and died faster under larger DTR around the same mean temperature. Large DTR (20 °C) decreased the probability of midgut infection, but not duration of the virus extrinsic incubation period (EIP), compared with moderate DTR (10 °C) or constant temperature. A thermodynamic model predicted that at mean temperatures 18 °C, larger DTR reduces DENV transmission. The negative impact of DTR on Ae. aegypti survival indicates that large temperature fluctuations will reduce the probability of vector survival through EIP and expectation of infectious life. Seasonal variation in the amplitude of daily temperature fluctuations helps to explain seasonal forcing of DENV transmission at locations where average temperature does not vary seasonally and mosquito abundance is not associated with dengue incidence. Mosquitoes lived longer and were more likely to become infected under moderate temperature fluctuations, which is typical of the high DENV transmission season than under large temperature fluctuations, which is typical of the low DENV transmission season. Our findings reveal the importance of considering short-term temperature variations when studying DENV transmission dynamics.
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            An evolutionary conserved function of the JAK-STAT pathway in anti-dengue defense.

            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.
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              STAMP: a web tool for exploring DNA-binding motif similarities

              STAMP is a newly developed web server that is designed to support the study of DNA-binding motifs. STAMP may be used to query motifs against databases of known motifs; the software aligns input motifs against the chosen database (or alternatively against a user-provided dataset), and lists of the highest-scoring matches are returned. Such similarity-search functionality is expected to facilitate the identification of transcription factors that potentially interact with newly discovered motifs. STAMP also automatically builds multiple alignments, familial binding profiles and similarity trees when more than one motif is inputted. These functions are expected to enable evolutionary studies on sets of related motifs and fixed-order regulatory modules, as well as illustrating similarities and redundancies within the input motif collection. STAMP is a highly flexible alignment platform, allowing users to ‘mix-and-match’ between various implemented comparison metrics, alignment methods (local or global, gapped or ungapped), multiple alignment strategies and tree-building methods. Motifs may be inputted as frequency matrices (in many of the commonly used formats), consensus sequences, or alignments of known binding sites. STAMP also directly accepts the output files from 12 supported motif-finders, enabling quick interpretation of motif-discovery analyses. STAMP is available at http://www.benoslab.pitt.edu/stamp
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                27 November 2012
                : 7
                : 11
                : e50512
                Affiliations
                [1 ]Program in Public Health, University of California Irvine, Irvine, California, United States of America
                [2 ]Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, California, United States of America
                [3 ]Institute for Genomics and Bioinformatics, University of California Irvine, Irvine, California, United States of America
                [4 ]Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America
                [5 ]Department of Microbiology and Molecular Genetics, University of California Irvine, Irvine, California, United States of America
                Centro de Pesquisas René Rachou, Brazil
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MB WAD CLC KEO OM AAJ. Performed the experiments: MB WAD CLC. Analyzed the data: MB WAD CLC KEO OM AAJ. Contributed reagents/materials/analysis tools: MB WAD CLC. Wrote the paper: MB WAD CLC KEO OM AAJ.

                Article
                PONE-D-12-19714
                10.1371/journal.pone.0050512
                3507784
                23209765
                90f2364e-952a-47e5-8470-08e0a1f7b40b
                Copyright @ 2012

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 5 July 2012
                : 22 October 2012
                Page count
                Pages: 14
                Funding
                This work was supported by grant U54AI065359 from the National Institute of Allergy and Infectious Diseases. WAD is supported in part by T15LM07443 from the National Library of Medicine, United States National Institutes of Health (NIH). C.L. Campbell and K.E. Olson are supported in part by a grant to the Regents of the University of California from the Foundation for the NIH through the Grand Challenges in Global Health initiative. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Computational Biology
                Genomics
                Genome Analysis Tools
                Transcriptomes
                Genetics
                Gene Expression
                Genomics
                Genome Analysis Tools
                Transcriptomes
                Genome Expression Analysis
                Microbiology
                Vector Biology
                Mosquitoes
                Emerging Infectious Diseases
                Host-Pathogen Interaction
                Virology
                Medicine
                Infectious Diseases
                Neglected Tropical Diseases
                Dengue Fever

                Uncategorized
                Uncategorized

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