Integrative proteomics and lipidomics reveals dual roles for lipid droplets in the host cell antiviral response

Integrative proteomics and lipidomics reveals dual roles for lipid droplets in the host cell antiviral response | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Integrative proteomics and lipidomics reveals dual roles for lipid droplets in the host cell antiviral response Karla helbig, Ebony Monson, Zahra Telikani, Jay Laws, Abbey Milligan, and 14 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7006641/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Lipid droplets (LDs), once viewed as inert lipid storage sites, are now recognised as dynamic organelles central to cellular signalling and immunity. This study presents a dual-omics approach, integrating proteomics and lipidomics, to investigate LDs in the host antiviral response. In vivo and in vitro RNA viral infection models demonstrate that LDs rapidly remodel both their proteome and lipidome. The antiviral proteins RIG-I, MDA5, STAT1, STAT2, and viperin are specifically recruited to virus-induced LDs. Simultaneously, the LD lipidome shifts toward enrichment in long-chain polyunsaturated fatty acids and bioactive phospholipids, likely enhancing membrane dynamics and protein recruitment. Enzymes involved in lipid metabolism and post-translational modifications are also upregulated, suggesting a mechanistic link between lipid remodeling and protein localisation. Functional assays utilizing artificial LDs revealed that arachidonic-acid and eicosapentaenoic-acid suppress viral replication and enhance type I and III interferon responses. These findings position LDs as key immunometabolic platforms in early antiviral defence. Biological sciences/Cell biology/Organelles Biological sciences/Microbiology/Virology Biological sciences/Immunology/Innate immunity lipid droplets virus RNA lipidomics proteomics dual omics signalling antiviral innate immunity Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SuplementaryTableS2dsRNALDproteomeOntology.pdf Table S2. Proteins identified in dsRNA stimulated astrocyte cells. SuplementaryTableS3ZIKVLDproteome.pdf Table S3. Proteins identified in ZIKV infected astrocyte cells. SuplementaryTableS4lipidome.pdf Table S4. All lipids identified in astrocyte cells. SuplementaryTableS1LCMVLDproteome.pdf Table S1. Proteins identified in LCMV infected brains. Movie2.mp4 Movie S2. Lipid droplet and mitochondria tracking following dsRNA stimulation. SupplimentaryMaterials.docx Supplementary Information and Figures Movie4.mp4 Movie S4. Lipid droplet and mitochondria tracking following oleic acid treatment. Movie1.mp4 Movie S1. Lipid droplet and mitochondria tracking in mock conditions. Movie3.mp4 Movie S3. Lipid droplet and mitochondria tracking following ZIKV infection. Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7006641","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":478426086,"identity":"fceda744-8e73-4b2f-933d-3473ed48617a","order_by":0,"name":"Karla 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