{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:38:49Z","timestamp":1790761129573,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T00:00:00Z","timestamp":1687132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["resjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Insect Molecular Biology"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Chikungunya virus (CHIKV) is an alphavirus that has re\u2010emerged globally over the last two decades and has the potential to become endemic in the United States due to the presence of competent mosquito vectors,\n                    <jats:italic>Aedes aegypti<\/jats:italic>\n                    and\n                    <jats:italic>Aedes albopictus<\/jats:italic>\n                    . CHIK disease is characterised by fever, rash, and joint pain, and causes chronic debilitating joint pain and swelling in &gt;50% of infected individuals. Given the disease severity caused by CHIKV and the global presence of vectors to facilitate its spread, strategies to reduce viral transmission are desperately needed; however, the human biological factors driving CHIKV transmission are poorly understood. Towards that end, we have previously shown that mosquitoes fed on alphavirus\u2010infected obese mice have reduced infection and transmission rates compared to those fed on infected lean mice despite similar viremia in lean and obese mice. One of the many host factors that increase in obese hosts is insulin, which was previously shown to impact the infection of mosquitoes by several flaviviruses. However, insulin's impact on alphavirus infection of live mosquitoes is unknown and whether insulin influences mosquito\u2010borne virus transmission has not been tested. To test this, we exposed\n                    <jats:italic>A. aegypti<\/jats:italic>\n                    mosquitoes to bloodmeals with CHIKV in the presence or absence of physiologically relevant levels of insulin and found that insulin significantly lowered both infection and transmission rates. RNA sequencing analysis on mosquito midguts isolated at 1\u2010day\u2010post\u2010infectious\u2010bloodmeal (dpbm) showed enrichment in genes in the Toll immune pathway in the presence of insulin, which was validated by reverse transcription\u2010quantitative polymerase chain reaction (RT\u2010qPCR). We then sought to determine if the Toll pathway plays a role in CHIKV infection of\n                    <jats:italic>Ae. aegypti<\/jats:italic>\n                    mosquitoes; therefore, we knocked down\n                    <jats:italic>Myd88<\/jats:italic>\n                    , a critical immune adaptor molecule for the Toll pathway, in live mosquitoes, and found increased CHIKV infection compared to the mock knockdown control group. Overall, these data demonstrate that insulin reduces CHIKV transmission by\n                    <jats:italic>Ae. aegypti<\/jats:italic>\n                    and activates the Toll pathway in mosquitoes, suggesting that conditions resulting in higher serum insulin concentrations may reduce alphavirus transmission. Finally, these studies suggest that strategies to activate insulin or Toll signalling in mosquitoes may be an effective control strategy against medically relevant alphaviruses.\n                  <\/jats:p>","DOI":"10.1111\/imb.12863","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T07:03:50Z","timestamp":1687158230000},"page":"648-657","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Insulin reduces the transmission potential of chikungunya virus and activates the toll pathway in\n                    <i>Aedes aegypti<\/i>\n                    mosquitoes"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7109-6132","authenticated-orcid":false,"given":"Pallavi","family":"Rai","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology Virginia Tech, VA\u2010MD College of Veterinary Medicine  Blacksburg Virginia USA"},{"name":"Center for Emerging, Zoonotic, and Arthropod\u2010borne Pathogens Virginia Tech  Blacksburg Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily M.","family":"Webb","sequence":"additional","affiliation":[{"name":"Center for Emerging, Zoonotic, and Arthropod\u2010borne Pathogens Virginia Tech  Blacksburg Virginia USA"},{"name":"Department of Entomology, Fralin Life Sciences Institute Virginia Tech  Blacksburg Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology Virginia Tech, VA\u2010MD College of Veterinary Medicine  Blacksburg Virginia USA"},{"name":"Biomedical Research Edward Via College of Osteopathic Medicine  Monroe Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Weger\u2010Lucarelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology Virginia Tech, VA\u2010MD College of Veterinary Medicine  Blacksburg Virginia USA"},{"name":"Center for Emerging, Zoonotic, and Arthropod\u2010borne Pathogens Virginia Tech  Blacksburg Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,19]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"What are normal levels of insulin?","author":"Advisor N.H.","year":"2022"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.10.029"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu638"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(16)00073-6"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/imb.12273"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1412984112"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-021-06766-3"},{"key":"e_1_2_9_9_1","unstructured":"Control E.C.F.D.P.A.(2023)Aedes aegypti\u2014factsheet for experts. 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