{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:54:16Z","timestamp":1792166056663,"version":"4.4.0"},"reference-count":51,"publisher":"National Academy of Sciences","issue":"44","license":[{"start":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T00:00:00Z","timestamp":1618963200000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/501100001349","name":"MOH | National Medical Research Council","doi-asserted-by":"publisher","award":["NMRC\/ZRRF\/0007\/2017"],"award-info":[{"award-number":["NMRC\/ZRRF\/0007\/2017"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001459","name":"Ministry of Education - Singapore","doi-asserted-by":"publisher","award":["MOE2015-T3-1-003"],"award-info":[{"award-number":["MOE2015-T3-1-003"]}],"id":[{"id":"10.13039\/501100001459","id-type":"DOI","asserted-by":"publisher"}]},{"name":"PHC - France","award":["6.01.18"],"award-info":[{"award-number":["6.01.18"]}]},{"DOI":"10.13039\/501100001348","name":"Agency for Science, Technology and Research","doi-asserted-by":"publisher","award":["core funding"],"award-info":[{"award-number":["core funding"]}],"id":[{"id":"10.13039\/501100001348","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,11,3]]},"abstract":"<jats:p>Dengue virus (DENV) subdues cell membranes for its cellular cycle by reconfiguring phospholipids in humans and mosquitoes. Here, we determined how and why DENV reconfigures phospholipids in the mosquito vector. By inhibiting and activating the de novo phospholipid biosynthesis, we demonstrated the antiviral impact of de novo\u2013produced phospholipids. In line with the virus hijacking lipids for its benefit, metabolomics analyses indicated that DENV actively inhibited the de novo phospholipid pathway and instead triggered phospholipid remodeling. We demonstrated the early induction of remodeling during infection by using isotope tracing in mosquito cells. We then confirmed in mosquitoes the antiviral impact of de novo phospholipids by supplementing infectious blood meals with a de novo phospholipid precursor. Eventually, we determined that phospholipid reconfiguration was required for viral genome replication but not for the other steps of the virus cellular cycle. Overall, we now propose that DENV reconfigures phospholipids through the remodeling cycle to modify the endomembrane and facilitate formation of the replication complex. Furthermore, our study identified de novo phospholipid precursor as a blood determinant of DENV human-to-mosquito transmission.<\/jats:p>","DOI":"10.1073\/pnas.2015095117","type":"journal-article","created":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T20:15:31Z","timestamp":1603311331000},"page":"27627-27636","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":49,"title":["Mosquito metabolomics reveal that dengue virus replication requires phospholipid reconfiguration via the remodeling cycle"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3347-7342","authenticated-orcid":false,"given":"Thomas","family":"Vial","sequence":"first","affiliation":[{"name":"Programme in Emerging Infectious Diseases, Duke-NUS Medical School, 169857, Singapore;"},{"name":"UMR 152 PHARMADEV-IRD, Universit\u00e9 Paul Sabatier-Toulouse 3, 31400, Toulouse, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8556-3395","authenticated-orcid":false,"given":"Wei-Lian","family":"Tan","sequence":"additional","affiliation":[{"name":"Programme in Emerging Infectious Diseases, Duke-NUS Medical School, 169857, Singapore;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Deharo","sequence":"additional","affiliation":[{"name":"UMR 152 PHARMADEV-IRD, Universit\u00e9 Paul Sabatier-Toulouse 3, 31400, Toulouse, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doroth\u00e9e","family":"Miss\u00e9","sequence":"additional","affiliation":[{"name":"MIVEGEC, IRD, CNRS, University of Montpellier, 34394, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6321-9005","authenticated-orcid":false,"given":"Guillaume","family":"Marti","sequence":"additional","affiliation":[{"name":"UMR 152 PHARMADEV-IRD, Universit\u00e9 Paul Sabatier-Toulouse 3, 31400, Toulouse, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1110-9039","authenticated-orcid":false,"given":"Julien","family":"Pompon","sequence":"additional","affiliation":[{"name":"Programme in Emerging Infectious Diseases, Duke-NUS Medical School, 169857, Singapore;"},{"name":"MIVEGEC, IRD, CNRS, University of Montpellier, 34394, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,10,21]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12060"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/sdata.2015.35"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/v6010069"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/v3020160"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.7b00719"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00118-14"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2019.09.015"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1153264"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.12919"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02531874"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/iub.354"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12860-014-0043-3"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/tra.12230"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.390997"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3420057"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-020518-114444"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.114454"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2736(02)00461-3"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7400410"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2330"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2009.03.007"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006853"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008199"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002373"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M005786200"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3390291"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24122208"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.3390\/metabo10010033"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1139\/O07-006"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R700019-JLR200"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1105\/tpc.112.104604"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2013.10.001"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2011.00267.x"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/4829180"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002584"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004449"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2015.12.011"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004607"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.017350"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007029"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1010811107"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1186\/1756-3305-5-148"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02445-08"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2009.01.005"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.43.10.4977-4983.2005"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aab3369"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3393"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.6b00770"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-007-0082-2"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0358-2"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky310"}],"updated-by":[{"DOI":"10.1073\/pnas.2217609119","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T00:00:00Z","timestamp":1667520000000}}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.2015095117","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2015095117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T14:00:52Z","timestamp":1667570452000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2015095117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,21]]},"references-count":51,"journal-issue":{"issue":"44","published-print":{"date-parts":[[2020,11,3]]}},"alternative-id":["10.1073\/pnas.2015095117"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2015095117","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,21]]},"assertion":[{"value":"2020-10-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}