{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:38:51Z","timestamp":1790761131759,"version":"4.1.0"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T00:00:00Z","timestamp":1635206400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T00:00:00Z","timestamp":1635206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["AWD05009_MOD0030"],"award-info":[{"award-number":["AWD05009_MOD0030"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Parasites Vectors"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Mosquito-borne dengue virus (DENV) causes major disease worldwide, impacting 50\u2013100 million people every year, and is spread by the major mosquito vector\n                      <jats:italic>Aedes aegypti<\/jats:italic>\n                      . Understanding mosquito physiology, including antiviral mechanisms, and developing new control strategies have become an important step towards the elimination of DENV disease. In the study reported here, we focused on autophagy, a pathway suggested as having a positive influence on virus replication in humans, as a potential antiviral target in the mosquito.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To understand the role played by autophagy in\n                      <jats:italic>Ae. aegypti<\/jats:italic>\n                      , we examined the activation of this pathway in Aag-2 cells, an\n                      <jats:italic>Ae. aegypti<\/jats:italic>\n                      -derived cell line, infected with DENV. Rapamycin and 3-methyladenine, two small molecules that have been shown to affect the function of the autophagy pathway, were used to activate or suppress, respectively, the autophagy pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At 1-day post-DENV infection in Aag-2 cells, transcript levels of both the microtubule-associated protein light chain 3-phosphatidylethanolamine conjugate (LC3-II) and autophagy-related protein 1 (ATG1) increased. Rapamycin treatment activated the autophagy pathway as early as 1-h post-treatment, and the virus titer had decreased in the Aag-2 cells at 2\u00a0days post-infection; in contrast, the 3-methyladenine treatment did not significantly affect the DENV titer. Treatment with these small molecules also impacted the ATG12 transcript levels in DENV-infected cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our studies revealed that activation of the autophagy pathway through rapamycin treatment altered DENV infection in the mosquito cells, suggesting that this pathway could be a possible antiviral mechanism in the mosquito system. Here we provide fundamental information needed to proceed with future experiments and to improve our understanding of the mosquito\u2019s immune response against DENV.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s13071-021-05066-w","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T12:03:20Z","timestamp":1635249800000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Activation of the autophagy pathway decreases dengue virus infection in Aedes aegypti cells"],"prefix":"10.1186","volume":"14","author":[{"given":"Tse-Yu","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea T.","family":"Smartt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,26]]},"reference":[{"key":"5066_CR1","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1126\/science.3277268","volume":"239","author":"S Halstead","year":"1988","unstructured":"Halstead S. Pathogenesis of dengue: challenges to molecular biology. Science. 1988;239:476.","journal-title":"Science"},{"key":"5066_CR2","unstructured":"World Health Organization. Dengue and severe dengue. 2021. http:\/\/www.who.int\/news-room\/fact-sheets\/detail\/dengue-and-severe-dengue"},{"key":"5066_CR3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001760","volume":"6","author":"OJ Brady","year":"2012","unstructured":"Brady OJ, Gething PW, Bhatt S, Messina JP, Brownstein JS, Hoen AG, et al. Refining the global spatial limits of dengue virus transmission by evidence-based consensus. PLoS Negl Trop Dis. 2012;6: e1760.","journal-title":"PLoS Negl Trop Dis"},{"key":"5066_CR4","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/path.2697","volume":"221","author":"D Glick","year":"2010","unstructured":"Glick D, Barth S, Macleod KF. Autophagy: cellular and molecular mechanisms. J Pathol. 2010;221:3\u201312.","journal-title":"J Pathol"},{"key":"5066_CR5","doi-asserted-by":"publisher","first-page":"2861","DOI":"10.1101\/gad.1599207","volume":"21","author":"N Mizushima","year":"2007","unstructured":"Mizushima N. Autophagy: process and function. Genes Dev. 2007;21:2861\u201373.","journal-title":"Genes Dev"},{"key":"5066_CR6","doi-asserted-by":"publisher","first-page":"160","DOI":"10.4161\/auto.3653","volume":"3","author":"T Yorimitsu","year":"2007","unstructured":"Yorimitsu T, Klionsky DJ. Endoplasmic reticulum stress: a new pathway to induce autophagy. Autophagy. 2007;3:160\u20132.","journal-title":"Autophagy"},{"key":"5066_CR7","doi-asserted-by":"publisher","first-page":"4035","DOI":"10.1074\/jbc.M512283200","volume":"281","author":"J Iwata","year":"2006","unstructured":"Iwata J, Ezaki J, Komatsu M, Yokota S, Ueno T, Tanida I, et al. Excess peroxisomes are degraded by autophagic machinery in mammals. J Biol Chem. 2006;281:4035\u201341.","journal-title":"J Biol Chem"},{"key":"5066_CR8","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.abb.2007.03.034","volume":"462","author":"I Kim","year":"2007","unstructured":"Kim I, Rodriguez-Enriquez S, Lemasters JJ. Selective degradation of mitochondria by mitophagy. Arch Biochem Biophys. 2007;462:245\u201353.","journal-title":"Arch Biochem Biophys"},{"key":"5066_CR9","doi-asserted-by":"publisher","first-page":"97","DOI":"10.3389\/fimmu.2013.00097","volume":"4","author":"E-K Jo","year":"2013","unstructured":"Jo E-K, Yuk J-M, Shin D-M, Sasakawa C. Roles of autophagy in elimination of intracellular bacterial pathogens. Front Immunol. 2013;4:97.","journal-title":"Front Immunol"},{"key":"5066_CR10","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1042\/bse0550153","volume":"55","author":"T Wileman","year":"2013","unstructured":"Wileman T. Autophagy as a defence against intracellular pathogens. Essays Biochem. 2013;55:153\u201363.","journal-title":"Essays Biochem"},{"key":"5066_CR11","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.cell.2014.02.049","volume":"157","author":"DR Green","year":"2014","unstructured":"Green DR, Levine B. To be or not to be? How selective autophagy and cell death govern cell fate. Cell. 2014;157:65\u201375.","journal-title":"Cell"},{"key":"5066_CR12","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1002\/path.2694","volume":"221","author":"S Barth","year":"2010","unstructured":"Barth S, Glick D, Macleod KF. Autophagy: assays and artifacts. J Pathol. 2010;221:117\u201324.","journal-title":"J Pathol"},{"key":"5066_CR13","doi-asserted-by":"publisher","first-page":"445","DOI":"10.4161\/auto.19496","volume":"8","author":"DJ Klionsky","year":"2012","unstructured":"Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K, et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2012;8:445\u2013544.","journal-title":"Autophagy"},{"key":"5066_CR14","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.1126\/science.290.5497.1717","volume":"290","author":"DJ Klionsky","year":"2000","unstructured":"Klionsky DJ, Emr SD. Cell biology\u2014autophagy as a regulated pathway of cellular degradation. Science. 2000;290:1717\u201321.","journal-title":"Science"},{"key":"5066_CR15","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1002\/rmv.630","volume":"19","author":"SB Kudchodkar","year":"2009","unstructured":"Kudchodkar SB, Levine B. Viruses and autophagy. Rev Med Virol. 2009;19:359\u201378.","journal-title":"Rev Med Virol"},{"key":"5066_CR16","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1038\/nri3532","volume":"13","author":"V Deretic","year":"2013","unstructured":"Deretic V, Saitoh T, Akira S. Autophagy in infection, inflammation and immunity. Nat Rev Immunol. 2013;13:722\u201337.","journal-title":"Nat Rev Immunol"},{"key":"5066_CR17","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1038\/ni.1634","volume":"9","author":"T Yano","year":"2008","unstructured":"Yano T, Mita S, Ohmori H, Oshima Y, Fujimoto Y, Ueda R, et al. Autophagic control of listeria through intracellular innate immune recognition in Drosophila. Nat Immunol. 2008;9:908\u201316.","journal-title":"Nat Immunol"},{"key":"5066_CR18","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1016\/j.immuni.2009.02.009","volume":"30","author":"S Shelly","year":"2009","unstructured":"Shelly S, Lukinova N, Bambina S, Berman A, Cherry S. Autophagy is an essential component of Drosophila immunity against vesicular stomatitis virus. Immunity. 2009;30:588\u201398.","journal-title":"Immunity"},{"key":"5066_CR19","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1159\/000350326","volume":"5","author":"RH Moy","year":"2013","unstructured":"Moy RH, Cherry S. Antimicrobial autophagy: a conserved innate immune response in Drosophila. J Innate Immun. 2013;5:444\u201355.","journal-title":"J Innate Immun"},{"key":"5066_CR20","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.3390\/v3081332","volume":"3","author":"NS Heaton","year":"2011","unstructured":"Heaton NS, Randall G. Dengue virus and autophagy. Viruses. 2011;3:1332\u201341.","journal-title":"Viruses"},{"key":"5066_CR21","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.virol.2008.02.016","volume":"374","author":"YR Lee","year":"2008","unstructured":"Lee YR, Lei HY, Liu MT, Wang JR, Chen SH, Jiang-Shieh YF, et al. Autophagic machinery activated by dengue virus enhances virus replication. Virology. 2008;374:240\u20138.","journal-title":"Virology"},{"key":"5066_CR22","doi-asserted-by":"publisher","first-page":"22147","DOI":"10.1074\/jbc.M110.192500","volume":"286","author":"JE McLean","year":"2011","unstructured":"McLean JE, Wudzinska A, Datan E, Quaglino D, Zakeri Z. Flavivirus NS4A-induced autophagy protects cells against death and enhances virus replication. J Biol Chem. 2011;286:22147\u201359.","journal-title":"J Biol Chem"},{"key":"5066_CR23","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.chom.2010.10.006","volume":"8","author":"NS Heaton","year":"2010","unstructured":"Heaton NS, Randall G. Dengue virus-induced autophagy regulates lipid metabolism. Cell Host Microbe. 2010;8:422\u201332.","journal-title":"Cell Host Microbe"},{"key":"5066_CR24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004828","volume":"10","author":"H-R Chen","year":"2016","unstructured":"Chen H-R, Chuang Y-C, Lin Y-S, Liu H-S, Liu C-C, Perng G-C, et al. Dengue virus nonstructural protein 1 induces vascular leakage through macrophage migration inhibitory factor and autophagy. PLoS Negl Trop Dis. 2016;10: e0004828.","journal-title":"PLoS Negl Trop Dis"},{"key":"5066_CR25","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1038\/s41598-017-18909-3","volume":"8","author":"Y-R Lee","year":"2018","unstructured":"Lee Y-R, Kuo S-H, Lin C-Y, Fu P-J, Lin Y-S, Yeh T-M, et al. Dengue virus-induced ER stress is required for autophagy activation, viral replication, and pathogenesis both in vitro and in vivo. Sci Rep. 2018;8:489.","journal-title":"Sci Rep"},{"key":"5066_CR26","doi-asserted-by":"publisher","first-page":"4921","DOI":"10.1016\/j.jmb.2013.10.006","volume":"425","author":"MB Kingsolver","year":"2013","unstructured":"Kingsolver MB, Huang ZJ, Hardy RW. Insect antiviral innate immunity: pathways, effectors, and connections. J Mol Biol. 2013;425:4921\u201336.","journal-title":"J Mol Biol"},{"key":"5066_CR27","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.ibmb.2016.07.004","volume":"76","author":"MW Eng","year":"2016","unstructured":"Eng MW, Zuylen MN, Severson DW. Apoptosis-related genes control autophagy and influence DENV-2 infection in the mosquito vector, Aedes aegypti. Insect Biochem Mol Biol. 2016;76:70\u201383.","journal-title":"Insect Biochem Mol Biol"},{"key":"5066_CR28","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.cmet.2014.01.001","volume":"19","author":"J Li","year":"2014","unstructured":"Li J, Kim SG, Blenis J. Rapamycin: one drug, many effects. Cell Metab. 2014;19:373\u20139.","journal-title":"Cell Metab"},{"key":"5066_CR29","doi-asserted-by":"publisher","first-page":"1992","DOI":"10.1091\/mbc.e08-12-1249","volume":"20","author":"CH Jung","year":"2009","unstructured":"Jung CH, Jun CB, Ro S-H, Kim Y-M, Otto NM, Cao J, et al. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell. 2009;20:1992\u20132003.","journal-title":"Mol Biol Cell"},{"key":"5066_CR30","doi-asserted-by":"publisher","first-page":"e2127","DOI":"10.1038\/cddis.2015.409","volume":"7","author":"E Datan","year":"2016","unstructured":"Datan E, Roy SG, Germain G, Zali N, McLean JE, Golshan G, et al. Dengue-induced autophagy, virus replication and protection from cell death require ER stress (PERK) pathway activation. Cell Death Dis. 2016;7:e2127\u2013e2127.","journal-title":"Cell Death Dis"},{"key":"5066_CR31","doi-asserted-by":"publisher","first-page":"1889","DOI":"10.1073\/pnas.79.6.1889","volume":"79","author":"PO Seglen","year":"1982","unstructured":"Seglen PO, Gordon PB. 3-Methyladenine: specific inhibitor of autophagic\/lysosomal protein degradation in isolated rat hepatocytes. Proc Natl Acad Sci USA. 1982;79:1889.","journal-title":"Proc Natl Acad Sci USA"},{"key":"5066_CR32","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1042\/bj3510095","volume":"351","author":"SP Davies","year":"2000","unstructured":"Davies SP, Reddy H, Caivano M, Cohen P. Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000;351:95\u2013105.","journal-title":"Biochem J"},{"key":"5066_CR33","doi-asserted-by":"publisher","first-page":"10850","DOI":"10.1074\/jbc.M109.080796","volume":"285","author":"YT Wu","year":"2010","unstructured":"Wu YT, Tan HL, Shui GH, Bauvy C, Huang Q, Wenk MR, et al. Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase. J Biol Chem. 2010;285:10850\u201361.","journal-title":"J Biol Chem"},{"key":"5066_CR34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0006715","volume":"12","author":"J-C Kao","year":"2018","unstructured":"Kao J-C, HuangFu W-C, Tsai T-T, Ho M-R, Jhan M-K, Shen T-J, et al. The antiparasitic drug niclosamide inhibits dengue virus infection by interfering with endosomal acidification independent of mTOR. PLoS Negl Trop Dis. 2018;12: e0006715.","journal-title":"PLoS Negl Trop Dis"},{"key":"5066_CR35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025502","volume":"6","author":"B Bryant","year":"2011","unstructured":"Bryant B, Raikhel AS. Programmed autophagy in the fat body of Aedes aegypti is required to maintain egg maturation cycles. PLoS ONE. 2011;6: e25502.","journal-title":"PLoS ONE"},{"key":"5066_CR36","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1590\/0074-02760170182","volume":"112","author":"CT Smartt","year":"2017","unstructured":"Smartt CT, Shin D, Alto BW. Dengue serotype-specific immune response in Aedes aegypti and Aedes albopictus. Mem Inst Oswaldo Cruz. 2017;112:829\u201337.","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"5066_CR37","doi-asserted-by":"publisher","first-page":"258","DOI":"10.4269\/ajtmh.2009.81.258","volume":"81","author":"CT Smartt","year":"2009","unstructured":"Smartt CT, Richards SL, Anderson SL, Erickson JS. West Nile virus infection alters midgut gene expression in Culex pipiens quinquefasciatus Say (Diptera: Culicidae). Am J Trop Med Hyg. 2009;81:258\u201363.","journal-title":"Am J Trop Med Hyg"},{"key":"5066_CR38","doi-asserted-by":"publisher","first-page":"71","DOI":"10.3390\/insects12010071","volume":"12","author":"T-Y Chen","year":"2021","unstructured":"Chen T-Y, Smartt CT, Shin D. Permethrin resistance in Aedes aegypti affects aspects of vectorial capacity. Insects. 2021;12:71.","journal-title":"Insects"},{"key":"5066_CR39","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1111\/jvec.12116","volume":"39","author":"BW Alto","year":"2014","unstructured":"Alto BW, Smartt CT, Shin D, Bettinardi D, Malicoate J, Anderson SL, et al. Susceptibility of Florida Aedes aegypti and Aedes albopictus to dengue viruses from Puerto Rico. J Vector Ecol. 2014;39:406\u201313.","journal-title":"J Vector Ecol"},{"key":"5066_CR40","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1186\/1471-2164-15-513","volume":"15","author":"D Shin","year":"2014","unstructured":"Shin D, Civana A, Acevedo C, Smartt CT. Transcriptomics of differential vector competence: West Nile virus infection in two populations of Culex pipiens quinquefasciatus linked to ovary development. BMC Genomics. 2014;15:513.","journal-title":"BMC Genomics"},{"key":"5066_CR41","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1099\/vir.0.005355-0","volume":"90","author":"M Panyasrivanit","year":"2009","unstructured":"Panyasrivanit M, Khakpoor A, Wikan N, Smith DR. Co-localization of constituents of the dengue virus translation and replication machinery with amphisomes. J Gen Virol. 2009;90:448\u201356.","journal-title":"J Gen Virol"},{"key":"5066_CR42","doi-asserted-by":"publisher","first-page":"10626","DOI":"10.1073\/pnas.0403460101","volume":"101","author":"IA Hansen","year":"2004","unstructured":"Hansen IA, Attardo GM, Park JH, Peng Q, Raikhel AS. Target of rapamycin-mediated amino acid signaling in mosquito anautogeny. Proc Natl Acad Sci. 2004;101:10626\u201331.","journal-title":"Proc Natl Acad Sci"},{"key":"5066_CR43","doi-asserted-by":"publisher","first-page":"1638","DOI":"10.1073\/pnas.1203519109","volume":"109","author":"D Voronin","year":"2012","unstructured":"Voronin D, Cook DAN, Steven A, Taylor MJ. Autophagy regulates Wolbachia populations across diverse symbiotic associations. Proc Natl Acad Sci USA. 2012;109:1638\u201346.","journal-title":"Proc Natl Acad Sci USA"},{"key":"5066_CR44","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.virol.2011.07.010","volume":"418","author":"M Panyasrivanit","year":"2011","unstructured":"Panyasrivanit M, Greenwood MP, Murphy D, Isidoro C, Auewarakul P, Smith DR. Induced autophagy reduces virus output in dengue infected monocytic cells. Virology. 2011;418:74\u201384.","journal-title":"Virology"},{"key":"5066_CR45","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1016\/j.immuni.2012.03.003","volume":"36","author":"M Nakamoto","year":"2012","unstructured":"Nakamoto M, Moy RH, Xu J, Bambina S, Yasunaga A, Shelly SS, et al. Virus recognition by Toll-7 activates antiviral autophagy in Drosophila. Immunity. 2012;36:658\u201367.","journal-title":"Immunity"},{"key":"5066_CR46","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007754","volume":"14","author":"DE Brackney","year":"2020","unstructured":"Brackney DE, Correa MA, Cozens DW. The impact of autophagy on arbovirus infection of mosquito cells. PLOS Negl Trop Dis. 2020;14: e0007754.","journal-title":"PLOS Negl Trop Dis"},{"key":"5066_CR47","doi-asserted-by":"publisher","first-page":"5415","DOI":"10.1128\/JVI.00238-16","volume":"90","author":"O Lamiable","year":"2016","unstructured":"Lamiable O, Arnold J, de Faria IJDS, Olmo RP, Bergami F, Meignin C, et al. Analysis of the contribution of hemocytes and autophagy to Drosophila antiviral immunity. J Virol. 2016;90:5415\u201326.","journal-title":"J Virol"},{"key":"5066_CR48","doi-asserted-by":"publisher","first-page":"6680","DOI":"10.1038\/sj.onc.1204091","volume":"19","author":"M Hidalgo","year":"2000","unstructured":"Hidalgo M, Rowinsky EK. The rapamycin-sensitive signal transduction pathway as a target for cancer therapy. Oncogene. 2000;19:6680\u20136.","journal-title":"Oncogene"},{"key":"5066_CR49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009353","volume":"17","author":"Y Feng","year":"2021","unstructured":"Feng Y, Chen L, Gao L, Dong L, Wen H, Song X, et al. Rapamycin inhibits pathogen transmission in mosquitoes by promoting immune activation. PLoS Pathog. 2021;17: e1009353.","journal-title":"PLoS Pathog."},{"key":"5066_CR50","doi-asserted-by":"publisher","first-page":"4154","DOI":"10.4049\/jimmunol.1102739","volume":"189","author":"Y-C Lin","year":"2012","unstructured":"Lin Y-C, Kuo H-C, Wang J-S, Lin W-W. Regulation of inflammatory response by 3-methyladenine involves the coordinative actions on Akt and glycogen synthase kinase 3\u03b2 rather than autophagy. J Immunol. 2012;189:4154.","journal-title":"J Immunol"},{"key":"5066_CR51","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/S0092-8674(00)80710-2","volume":"97","author":"N Perrimon","year":"1999","unstructured":"Perrimon N, McMahon AP. Negative feedback mechanisms and their roles during pattern formation. Cell. 1999;97:13\u20136.","journal-title":"Cell"}],"container-title":["Parasites &amp; Vectors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13071-021-05066-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13071-021-05066-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13071-021-05066-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T14:17:28Z","timestamp":1635257848000},"score":1,"resource":{"primary":{"URL":"https:\/\/parasitesandvectors.biomedcentral.com\/articles\/10.1186\/s13071-021-05066-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,26]]},"references-count":51,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["5066"],"URL":"https:\/\/doi.org\/10.1186\/s13071-021-05066-w","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.04.06.438578","asserted-by":"object"}]},"ISSN":["1756-3305"],"issn-type":[{"value":"1756-3305","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,26]]},"assertion":[{"value":"20 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 October 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 October 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"551"}}