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      Sequential Infection of Aedes aegypti Mosquitoes with Chikungunya Virus and Zika Virus Enhances Early Zika Virus Transmission

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          Abstract

          In urban settings, chikungunya, Zika, and dengue viruses are transmitted by Aedes aegypti mosquitoes. Since these viruses co-circulate in several regions, coinfection in humans and vectors may occur, and human coinfections have been frequently reported. Yet, little is known about the molecular aspects of virus interactions within hosts and how they contribute to arbovirus transmission dynamics. We have previously shown that Aedes aegypti exposed to chikungunya and Zika viruses in the same blood meal can become coinfected and transmit both viruses simultaneously. However, mosquitoes may also become coinfected by multiple, sequential feeds on single infected hosts. Therefore, we tested whether sequential infection with chikungunya and Zika viruses impacts mosquito vector competence. We exposed Ae. aegypti mosquitoes first to one virus and 7 days later to the other virus and compared infection, dissemination, and transmission rates between sequentially and single infected groups. We found that coinfection rates were high after sequential exposure and that mosquitoes were able to co-transmit both viruses. Surprisingly, chikungunya virus coinfection enhanced Zika virus transmission 7 days after the second blood meal. Our data demonstrate heterologous arbovirus synergism within mosquitoes, by unknown mechanisms, leading to enhancement of transmission under certain conditions.

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          Most cited references34

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          Reemergence of chikungunya virus.

          T Morrison (2014)
          Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes acute fever and acute and chronic musculoskeletal pain in humans. Since 2004, CHIKV has caused millions of cases of disease in the Indian Ocean region and has emerged in new areas, including Europe, the Middle East, and the Pacific region. The mosquito vectors for this virus are globally distributed in tropical and temperate zones, providing the opportunity for CHIKV to continue to expand into new geographic regions. In October 2013, locally acquired cases of CHIKV infection were identified on the Caribbean island of Saint Martin, signaling the arrival of the virus in the Western Hemisphere. In just 9 months, CHIKV has spread to 22 countries in the Caribbean and Central and South America, resulting in hundreds of thousands of cases. CHIKV disease can be highly debilitating, and large epidemics have severe economic consequences. Thus, there is an urgent need for continued research into the epidemiology, pathogenesis, prevention, and treatment of these infections. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
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            A systematic approach to virus–virus interactions

            A virus–virus interaction is a measurable difference in the course of infection of one virus as a result of a concurrent or prior infection by a different species or strain of virus. Many such interactions have been discovered by chance, yet they have rarely been studied systematically. Increasing evidence suggests that virus–virus interactions are common and may be critical to understanding viral pathogenesis in natural hosts. In this review we propose a system for classifying virus–virus interactions by organizing them into three main categories: (1) direct interactions of viral genes or gene products, (2) indirect interactions that result from alterations in the host environment, and (3) immunological interactions. We have so far identified 15 subtypes of interaction and assigned each to one of these categories. It is anticipated that this framework will provide for a more systematic approach to investigating virus–virus interactions, both at the cellular and organismal levels.
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              Impact of simultaneous exposure to arboviruses on infection and transmission by Aedes aegypti mosquitoes

              The recent emergence of both chikungunya and Zika viruses in the Americas has significantly expanded their distribution and has thus increased the possibility that individuals may become infected by more than one Aedes aegypti-borne virus at a time. Recent clinical data support an increase in the frequency of coinfection in human patients, raising the likelihood that mosquitoes could be exposed to multiple arboviruses during one feeding episode. The impact of coinfection on the ability of relevant vector species to transmit any of these viruses (that is, their vector competence) has not been determined. Thus, we here expose Ae. aegypti mosquitoes to chikungunya, dengue-2 or Zika viruses, both individually and as double and triple infections. Our results show that these mosquitoes can be infected with and can transmit all combinations of these viruses simultaneously. Importantly, infection, dissemination and transmission rates in mosquitoes are only mildly affected by coinfection.
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                Author and article information

                Journal
                Insects
                Insects
                insects
                Insects
                MDPI
                2075-4450
                01 December 2018
                December 2018
                : 9
                : 4
                : 177
                Affiliations
                Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA; lexir5394@ 123456gmail.com (A.R.); emceeyoung@ 123456gmail.com (M.C.Y.); William.Black@ 123456colostate.edu (W.C.B.IV); Brian.Foy@ 123456colostate.edu (B.D.F.); Gregory.Ebel@ 123456colostate.edu (G.D.E.)
                Author notes
                [* ]Correspondence: Tereza.Magalhaes@ 123456colostate.edu (T.M.); Claudia.Rueckert@ 123456Colostate.edu (C.R.); Tel.: +1-970-491-5699 (T.M.); +1-970-491-2202 (C.R.)
                Author information
                https://orcid.org/0000-0003-3732-6752
                Article
                insects-09-00177
                10.3390/insects9040177
                6315929
                30513725
                c884ed0f-35ed-45b6-9184-f57205f7f242
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 26 October 2018
                : 27 November 2018
                Categories
                Article

                mosquitoes,arboviruses,coinfection,chikungunya,zika,sequential infection

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