{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:12:23Z","timestamp":1792131143681,"version":"4.4.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010763","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T00:00:00Z","timestamp":1660780800000}}],"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T00:00:00Z","timestamp":1659916800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["MOH-000610-00"],"award-info":[{"award-number":["MOH-000610-00"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016017","name":"Duke-NUS Medical School","doi-asserted-by":"crossref","award":["Duke\/Duke-NUS\/RECA(Pilot)\/2019\/0047"],"award-info":[{"award-number":["Duke\/Duke-NUS\/RECA(Pilot)\/2019\/0047"]}],"id":[{"id":"10.13039\/100016017","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001381","name":"National Research Foundation Singapore","doi-asserted-by":"publisher","award":["NRFMOSTID21-0014"],"award-info":[{"award-number":["NRFMOSTID21-0014"]}],"id":[{"id":"10.13039\/501100001381","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001459","name":"Ministry of Education Singapore","doi-asserted-by":"crossref","award":["MOET32020-0002"],"award-info":[{"award-number":["MOET32020-0002"]}],"id":[{"id":"10.13039\/501100001459","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Transmembrane Protein 41B (TMEM41B) and Vacuole Membrane Protein 1 (VMP1) are two ER-associated lipid scramblases that play a role in autophagosome formation and cellular lipid metabolism. TMEM41B is also a recently validated host factor required by flaviviruses and coronaviruses. However, the exact underlying mechanism of TMEM41B in promoting viral infections remains an open question. Here, we validated that both TMEM41B and VMP1 are essential host dependency factors for all four serotypes of dengue virus (DENV) and human coronavirus OC43 (HCoV-OC43), but not chikungunya virus (CHIKV). While HCoV-OC43 failed to replicate entirely in both TMEM41B- and VMP1-deficient cells, we detected diminished levels of DENV infections in these cell lines, which were accompanied by upregulation of the innate immune dsRNA sensors, RIG-I and MDA5. Nonetheless, this upregulation did not correspondingly induce the downstream effector TBK1 activation and Interferon-beta expression. Despite low levels of DENV replication, classical DENV replication organelles were undetectable in the infected TMEM41B-deficient cells, suggesting that the upregulation of the dsRNA sensors is likely a consequence of aberrant viral replication rather than a causal factor for reduced DENV infection. Intriguingly, we uncovered that the inhibitory effect of TMEM41B deficiency on DENV replication, but not HCoV-OC43, can be partially reversed using exogenous fatty acid supplements. In contrast, VMP1 deficiency cannot be rescued using the metabolite treatment. In line with the observed phenotypes, we found that both TMEM41B- and VMP1-deficient cells harbor higher levels of compromised mitochondria, especially in VMP1 deficiency which results in severe dysregulations of mitochondrial beta-oxidation. Using a metabolomic profiling approach, we revealed distinctive global dysregulations of the cellular metabolome, particularly lipidome, in TMEM41B- and VMP1-deficient cells. Our findings highlight a central role for TMEM41B and VMP1 in modulating multiple cellular pathways, including lipid mobilization, mitochondrial beta-oxidation, and global metabolic regulations, to facilitate the replication of flaviviruses and coronaviruses.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010763","type":"journal-article","created":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T17:35:03Z","timestamp":1659980103000},"page":"e1010763","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":50,"title":["TMEM41B and VMP1 modulate cellular lipid and energy metabolism for facilitating dengue virus infection"],"prefix":"10.1371","volume":"18","author":[{"given":"Meisam","family":"Yousefi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai Suet","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biaoguo","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cythia Lingli","family":"Yong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Yap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwan Sing Leona","family":"Tay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dewei","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur Insyirah","family":"Nurazmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Linster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin J. D.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yie Hou","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan E.","family":"Carette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eng Eong","family":"Ooi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan Rong","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9014-1365","authenticated-orcid":true,"given":"Yaw Shin","family":"Ooi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,8,8]]},"reference":[{"key":"ppat.1010763.ref001","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/S0140-6736(14)60572-9","article-title":"Dengue.","volume":"385","author":"MG Guzman","year":"2015","journal-title":"Lancet"},{"key":"ppat.1010763.ref002","doi-asserted-by":"crossref","first-page":"6355","DOI":"10.1016\/j.vaccine.2017.09.089","article-title":"Dengvaxia sensitizes seronegatives to vaccine enhanced disease regardless of age","volume":"35","author":"SB Halstead","year":"2017","journal-title":"Vaccine"},{"key":"ppat.1010763.ref003","doi-asserted-by":"crossref","first-page":"l5710","DOI":"10.1136\/bmj.l5710","article-title":"Is Dengvaxia a useful vaccine for dengue endemic areas?","volume":"367","author":"DJ 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Available: https:\/\/www.thermofisher.com\/order\/catalog\/product\/R70007"},{"key":"ppat.1010763.ref054","doi-asserted-by":"crossref","first-page":"783","DOI":"10.47102\/annals-acadmedsg.V35N11p783","article-title":"Early Dengue infection and outcome study (EDEN)\u2014study design and preliminary findings.","volume":"35","author":"JGH Low","year":"2006","journal-title":"Ann Acad Med Singapore"},{"key":"ppat.1010763.ref055","doi-asserted-by":"crossref","first-page":"5416","DOI":"10.1038\/s41467-018-07901-8","article-title":"Optimized libraries for CRISPR-Cas9 genetic screens with multiple modalities.","volume":"9","author":"KR Sanson","year":"2018","journal-title":"Nat Commun"},{"key":"ppat.1010763.ref056","first-page":"2281","article-title":"Genome engineering using the CRISPR-Cas9 system.","volume":"8","author":"FA Ran","year":"2013","journal-title":"Nat Protoc 2013 811."},{"key":"ppat.1010763.ref057","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.celrep.2017.06.085","article-title":"DDX6 represses aberrant activation of interferon-stimulated genes","volume":"20","author":"JH Lumb","year":"2017","journal-title":"Cell Rep"},{"key":"ppat.1010763.ref058","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/nmeth.3047","article-title":"Improved vectors and genome-wide libraries for CRISPR screening.","volume":"11","author":"NE Sanjana","year":"2014","journal-title":"Nat Methods"},{"key":"ppat.1010763.ref059","doi-asserted-by":"crossref","first-page":"e6529","DOI":"10.1371\/journal.pone.0006529","article-title":"A Versatile Viral System for Expression and Depletion of Proteins in Mammalian Cells.","volume":"4","author":"E Campeau","year":"2009","journal-title":"PLoS One"},{"key":"ppat.1010763.ref060","unstructured":"V. R. Doubling Time Computing. 2006. Available: https:\/\/www.doubling-time.com\/compute.php"},{"key":"ppat.1010763.ref061","doi-asserted-by":"crossref","DOI":"10.1186\/gb-2006-7-10-r100","article-title":"CellProfiler: image analysis software for identifying and quantifying cell phenotypes","volume":"7","author":"AE Carpenter","year":"2006","journal-title":"Genome Biol"},{"key":"ppat.1010763.ref062","doi-asserted-by":"crossref","first-page":"e2005970","DOI":"10.1371\/journal.pbio.2005970","article-title":"CellProfiler 3.0: Next-generation image processing for biology","volume":"16","author":"C McQuin","year":"2018","journal-title":"PLOS Biol"},{"key":"ppat.1010763.ref063","doi-asserted-by":"crossref","first-page":"101297","DOI":"10.1016\/j.xpro.2022.101297","article-title":"A protocol to assess cellular bioenergetics in flavivirus-infected cells.","volume":"3","author":"JZH Low","year":"2022","journal-title":"STAR Protoc"},{"key":"ppat.1010763.ref064","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1194\/jlr.D700041-JLR200","article-title":"Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics","volume":"49","author":"V Matyash","year":"2008","journal-title":"J Lipid Res"},{"key":"ppat.1010763.ref065","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1021\/pr901094j","article-title":"Comprehensive LC-MS E lipidomic analysis using a shotgun approach and its application to biomarker detection and identification in osteoarthritis patients","volume":"9","author":"JM Castro-Perez","year":"2010","journal-title":"J Proteome Res"},{"key":"ppat.1010763.ref066","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-017-02086-y","article-title":"Allosteric pyruvate kinase-based \u201clogic gate\u201d synergistically senses energy and sugar levels in Mycobacterium tuberculosis.","volume":"8","author":"W Zhong","year":"2017","journal-title":"Nat Commun"},{"key":"ppat.1010763.ref067","doi-asserted-by":"crossref","first-page":"D463","DOI":"10.1093\/nar\/gkv1042","article-title":"Metabolomics Workbench: An international repository for metabolomics data and metadata, metabolite standards, protocols, tutorials and training, and analysis tools","volume":"44","author":"M Sud","year":"2016","journal-title":"Nucleic Acids Res"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1010763","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T00:00:00Z","timestamp":1660780800000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010763","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,25]],"date-time":"2023-11-25T11:49:29Z","timestamp":1700912969000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010763"}},"subtitle":[],"editor":[{"given":"Helen M.","family":"Lazear","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,8,8]]},"references-count":67,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1010763","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.ppat.1010763","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,8]]}}}