{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T15:05:04Z","timestamp":1790435104830,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010411","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T00:00:00Z","timestamp":1650326400000}}],"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T00:00:00Z","timestamp":1649030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"WSU College of Veterinary Medicine","award":["Stanley L. Adler research fund"],"award-info":[{"award-number":["Stanley L. Adler research fund"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32GM008336"],"award-info":[{"award-number":["T32GM008336"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Poncin Trust"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI151166"],"award-info":[{"award-number":["R01AI151166"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI151166"],"award-info":[{"award-number":["R01AI151166"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UI College of Agricultural and Life Sciences","award":["startup"],"award-info":[{"award-number":["startup"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    The recent global Zika epidemics have revealed the significant threat that mosquito-borne viruses pose. There are currently no effective vaccines or prophylactics to prevent Zika virus (ZIKV) infection. Limiting exposure to infected mosquitoes is the best way to reduce disease incidence. Recent studies have focused on targeting mosquito reproduction and immune responses to reduce transmission. Previous work has evaluated the effect of insulin signaling on antiviral JAK\/STAT and RNAi in vector mosquitoes. Specifically, insulin-fed mosquitoes resulted in reduced virus replication in an RNAi-independent, ERK-mediated JAK\/STAT-dependent mechanism. In this work, we demonstrate that targeting insulin signaling through the repurposing of small molecule drugs results in the activation of both RNAi and JAK\/STAT antiviral pathways. ZIKV-infected\n                    <jats:italic>Aedes aegypti<\/jats:italic>\n                    were fed blood containing demethylasterriquinone B1 (DMAQ-B1), a potent insulin mimetic, in combination with AKT inhibitor VIII. Activation of this coordinated response additively reduced ZIKV levels in\n                    <jats:italic>Aedes aegypti<\/jats:italic>\n                    . This effect included a quantitatively greater reduction in salivary gland ZIKV levels up to 11 d post-bloodmeal ingestion, relative to single pathway activation. Together, our study indicates the potential for field delivery of these small molecules to substantially reduce virus transmission from mosquito to human. As infections like Zika virus are becoming more burdensome and prevalent, understanding how to control this family of viruses in the insect vector is an important issue in public health.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010411","type":"journal-article","created":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T13:35:16Z","timestamp":1649079316000},"page":"e1010411","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":27,"title":["Coupled small molecules target RNA interference and JAK\/STAT signaling to reduce Zika virus infection in Aedes aegypti"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1698-883X","authenticated-orcid":true,"given":"Chasity E.","family":"Trammell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2818-6711","authenticated-orcid":true,"given":"Gabriela","family":"Ramirez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irma","family":"Sanchez-Vargas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"St Clair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oshani C.","family":"Ratnayake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5047-4683","authenticated-orcid":true,"given":"Shirley","family":"Luckhart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6798-2537","authenticated-orcid":true,"given":"Rushika","family":"Perera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6394-332X","authenticated-orcid":true,"given":"Alan G.","family":"Goodman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,4,4]]},"reference":[{"key":"ppat.1010411.ref001","first-page":"1","article-title":"Global spatial assessment of Aedes aegypti and Culex quinquefasciatus: a scenario of Zika virus exposure","volume":"147","author":"AJ Alaniz","year":"2018","journal-title":"Epidemiol Infect"},{"issue":"9","key":"ppat.1010411.ref002","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1590\/0074-02760160149","article-title":"Mapping the global geographic potential of Zika virus spread","volume":"111","author":"AM Samy","year":"2016","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"ppat.1010411.ref003","volume-title":"Implications for public health in the Americas","author":"Pan American Health Organization","year":"2015"},{"key":"ppat.1010411.ref004","volume-title":"PAHO\/WHO | Zika Cumulative Cases","author":"Pan American Health Organization","year":"2016"},{"issue":"1","key":"ppat.1010411.ref005","article-title":"Global outbreaks of zika infection by epidemic observatory (EpiWATCH), 2016\u20132019","volume":"2","author":"BS Bhargavi","year":"2020","journal-title":"Glob Biosecurity"},{"key":"ppat.1010411.ref006","doi-asserted-by":"crossref","first-page":"28792","DOI":"10.1038\/srep28792","article-title":"The wMel strain of Wolbachia Reduces Transmission of Zika virus by Aedes aegypti.","volume":"6","author":"MT Aliota","year":"2016","journal-title":"Sci Rep"},{"issue":"6","key":"ppat.1010411.ref007","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.chom.2016.04.021","article-title":"Wolbachia Blocks Currently Circulating Zika Virus Isolates in Brazilian Aedes aegypti Mosquitoes","volume":"19","author":"HLC Dutra","year":"2016","journal-title":"Cell Host Microbe"},{"issue":"3","key":"ppat.1010411.ref008","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.celrep.2018.12.068","article-title":"A Role for the Insulin Receptor in the Suppression of Dengue Virus and Zika Virus in Wolbachia-Infected Mosquito Cells","volume":"26","author":"G Haqshenas","year":"2019","journal-title":"Cell Rep"},{"issue":"7858","key":"ppat.1010411.ref009","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/d41586-021-01186-6","article-title":"First genetically modified mosquitoes released in the United States","volume":"593","author":"E. 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