{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T05:53:01Z","timestamp":1793166781502,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011975","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T00:00:00Z","timestamp":1712793600000}}],"reference-count":78,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI148477"],"award-info":[{"award-number":["AI148477"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Arboviruses can emerge rapidly and cause explosive epidemics of severe disease. Some of the most epidemiologically important arboviruses, including dengue virus (DENV), Zika virus (ZIKV), Chikungunya (CHIKV) and yellow fever virus (YFV), are transmitted by\n                    <jats:italic>Aedes<\/jats:italic>\n                    mosquitoes, most notably\n                    <jats:italic>Aedes aegypti<\/jats:italic>\n                    and\n                    <jats:italic>Aedes albopictus<\/jats:italic>\n                    . After a mosquito blood feeds on an infected host, virus enters the midgut and infects the midgut epithelium. The virus must then overcome a series of barriers before reaching the mosquito saliva and being transmitted to a new host. The virus must escape from the midgut (known as the midgut escape barrier; MEB), which is thought to be mediated by transient changes in the permeability of the midgut-surrounding basal lamina layer (BL) following blood feeding. Here, we present a mathematical model of the within-mosquito population dynamics of DENV (as a model system for mosquito-borne viruses more generally) that includes the interaction of the midgut and BL which can account for the MEB. Our results indicate a dose-dependency of midgut establishment of infection as well as rate of escape from the midgut: collectively, these suggest that the extrinsic incubation period (EIP)\u2014the time taken for DENV virus to be transmissible after infection\u2014is shortened when mosquitoes imbibe more virus. Additionally, our experimental data indicate that multiple blood feeding events, which more closely mimic mosquito-feeding behavior in the wild, can hasten the course of infections, and our model predicts that this effect is sensitive to the amount of virus imbibed. Our model indicates that mutations to the virus which impact its replication rate in the midgut could lead to even shorter EIPs when double-feeding occurs. Mechanistic models of within-vector viral infection dynamics provide a quantitative understanding of infection dynamics and could be used to evaluate novel interventions that target the mosquito stages of the infection.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1011975","type":"journal-article","created":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T13:50:12Z","timestamp":1711979412000},"page":"e1011975","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":29,"title":["Investigating the dose-dependency of the midgut escape barrier using a mechanistic model of within-mosquito dengue virus population dynamics"],"prefix":"10.1371","volume":"20","author":[{"given":"Rebecca M.","family":"Johnson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac J.","family":"Stopard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen M.","family":"Byrne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip M.","family":"Armstrong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas E.","family":"Brackney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4274-4158","authenticated-orcid":true,"given":"Ben","family":"Lambert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,4,1]]},"reference":[{"key":"ppat.1011975.ref001","unstructured":"World Health Organization. Dengue and severe dengue; January 10, 2022. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/dengue-and-severe-dengue."},{"key":"ppat.1011975.ref002","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nature22402","article-title":"Zika virus evolution and spread in the Americas","volume":"546","author":"HC Metsky","year":"2017","journal-title":"Nature"},{"key":"ppat.1011975.ref003","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/s41559-019-0836-z","article-title":"Vector-borne transmission and evolution of Zika virus","volume":"3","author":"G Guti\u00e9rrez-Bugallo","year":"2019","journal-title":"Nature Ecology & Evolution"},{"key":"ppat.1011975.ref004","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/s41564-020-0714-0","article-title":"The continued threat of emerging flaviviruses","volume":"5","author":"TC Pierson","year":"2020","journal-title":"Nature Microbiology"},{"key":"ppat.1011975.ref005","unstructured":"World Health Organization. Zika virus; August 22, 2023. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/zika-virus."},{"issue":"5","key":"ppat.1011975.ref006","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1038\/s41564-019-0376-y","article-title":"Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus","volume":"4","author":"MU Kraemer","year":"2019","journal-title":"Nature Microbiology"},{"key":"ppat.1011975.ref007","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.pt.2012.01.001","article-title":"Feeding strategies of anthropophilic mosquitoes result in increased risk of pathogen transmission","volume":"28","author":"TW Scott","year":"2012","journal-title":"Trends in Parasitology"},{"key":"ppat.1011975.ref008","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1603\/0022-2585-37.1.77","article-title":"Longitudinal Studies of Aedes aegypti (Diptera: Culicidae) in Thailand and Puerto Rico: Population Dynamics","volume":"37","author":"TW 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