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      Follow up of a robust meta-signature to identify Zika virus infection in Aedes aegypti: another brick in the wall

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          Abstract

          The mosquito Aedes aegypti is the main vector of several arthropod-borne diseases that have global impacts. In a previous meta-analysis, our group identified a vector gene set containing 110 genes strongly associated with infections of dengue, West Nile and yellow fever viruses. Of these 110 genes, four genes allowed a highly accurate classification of infected status. More recently, a new study of Ae. aegypti infected with Zika virus (ZIKV) was published, providing new data to investigate whether this “infection” gene set is also altered during a ZIKV infection. Our hypothesis is that the infection-associated signature may also serve as a proxy to classify the ZIKV infection in the vector. Raw data associated with the NCBI/BioProject were downloaded and re-analysed. A total of 18 paired-end replicates corresponding to three ZIKV-infected samples and three controls were included in this study. The nMDS technique with a logistic regression was used to obtain the probabilities of belonging to a given class. Thus, to compare both gene sets, we used the area under the curve and performed a comparison using the bootstrap method. Our meta-signature was able to separate the infected mosquitoes from the controls with good predictive power to classify the Zika-infected mosquitoes.

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          Most cited references11

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          First report of autochthonous transmission of Zika virus in Brazil

          In the early 2015, several cases of patients presenting symptoms of mild fever, rash, conjunctivitis and arthralgia were reported in the northeastern Brazil. Although all patients lived in a dengue endemic area, molecular and serological diagnosis for dengue resulted negative. Chikungunya virus infection was also discarded. Subsequently, Zika virus (ZIKV) was detected by reverse transcription-polymerase chain reaction from the sera of eight patients and the result was confirmed by DNA sequencing. Phylogenetic analysis suggests that the ZIKV identified belongs to the Asian clade. This is the first report of ZIKV infection in Brazil.
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            Local and regional spread of chikungunya fever in the Americas.

            Chikungunya fever (CHIKV), a viral disease transmitted by mosquitoes, is currently affecting several areas in the Caribbean. The vector is found in the Americas from southern Florida to Brazil, and the Caribbean is a highly connected region in terms of population movements. There is therefore a significant risk for the epidemic to quickly expand to a wide area in the Americas. Here, we describe the spread of CHIKV in the first three areas to report cases and between areas in the region. Local transmission of CHIKV in the Caribbean is very effective, the mean number of cases generated by a human case ranging from two to four. There is a strong spatial signature in the regional epidemic, with the risk of transmission between areas estimated to be inversely proportional to the distance rather than driven by air transportation. So far, this simple distance-based model has successfully predicted observed patterns of spread. The spatial structure allows ranking areas according to their risk of invasion. This characterisation may help national and international agencies to optimise resource allocation for monitoring and control and encourage areas with elevated risks to act.
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              Aedes aegypti Molecular Responses to Zika Virus: Modulation of Infection by the Toll and Jak/Stat Immune Pathways and Virus Host Factors

              Zika (ZIKV) and dengue virus (DENV) are transmitted to humans by Aedes mosquitoes. However, the molecular interactions between the vector and ZIKV remain largely unexplored. In this work, we further investigated the tropism of ZIKV in two different Aedes aegypti strains and show that the virus infection kinetics, tissue migration, and susceptibility to infection differ between mosquito strains. We also compare the vector transcriptome changes upon ZIKV or DENV infection demonstrating that 40% of the mosquito’s midgut infection-responsive transcriptome is virus-specific at 7 days after virus ingestion. Regulated genes included key factors of the mosquito’s anti-viral immunity. Comparison of the ZIKV and DENV infection-responsive transcriptome data to those available for yellow fever virus and West Nile virus identified 26 genes likely to play key roles in virus infection of Aedes mosquitoes. Through reverse genetic analyses, we show that the Toll and the Jak/Stat innate immune pathways mediate increased resistance to ZIKV infection, and the conserved DENV host factors vATPase and inosine-5′-monophosphate dehydrogenase are also utilized for ZIKV infection.
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                Author and article information

                Journal
                Mem Inst Oswaldo Cruz
                Mem. Inst. Oswaldo Cruz
                mioc
                Memórias do Instituto Oswaldo Cruz
                Instituto Oswaldo Cruz, Ministério da Saúde
                0074-0276
                1678-8060
                28 May 2018
                2018
                : 113
                : 6
                : e180053
                Affiliations
                [1 ]Fundação Oswaldo Cruz-Fiocruz, Instituto Gonçalo Moniz, Salvador, BA, Brasil
                [2 ]Fundação Oswaldo Cruz-Fiocruz, Programa de Pós-Graduação em Biotecnologia em Saúde Investigativa, Salvador, BA, Brasil
                [3 ]Universidade Federal da Bahia, Serviço de Imunologia, Salvador, BA, Brasil
                [4 ]Universidade Tecnológica Federal do Paraná, Cornélio Procópio, PR, Brasil
                [5 ]Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, SP, Brasil
                [6 ]Universidade Salvador, Salvador, BA, Brasil
                Author notes
                [+ ] Corresponding author: ferreirafk@ 123456gmail.com

                AUTHORS’ CONTRIBUTION

                EF, MR, JIK, CFA and ARP downloaded the data and performed the analysis; PIR, KFF and ATLQ wrote the manuscript.

                EF, MR, KFF, PIPR and ATLQ contributed equally to this work.

                Article
                00402
                10.1590/0074-02760180053
                5965457
                29846381
                1d576f30-4a6c-4cac-ae46-39c9be1f3902

                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 work is properly cited.

                History
                : 29 January 2018
                : 17 April 2018
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 23, Pages: NaN
                Categories
                Short Communication

                rna-seq,signature,transcriptome,zika virus
                rna-seq, signature, transcriptome, zika virus

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