Two Plasmodium vivax hypnozoite-expressed RNA-binding proteins inhibit liver stage replication

Two Plasmodium vivax hypnozoite-expressed RNA-binding proteins inhibit liver stage replication | 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 Two Plasmodium vivax hypnozoite-expressed RNA-binding proteins inhibit liver stage replication Stefan Kappe, Kim Chi Vo, Riëtte van Biljon, Gigliola Zanghi, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8080228/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 Plasmodium vivax (Pv) forms non-replicating liver stages called hypnozoites, which activate after primary infection, and cause relapses of symptomatic blood-stage malaria. We hypothesized that hypnozoites must actively suppress schizogony to maintain a quiescent state. Differential transcriptome prospecting idenfied two hypnozoite-expressed transcripts encoding putative RNA-binding proteins. We assessed the functional role of the two encoded proteins in Plasmodium yoelii (Py), a rodent malaria parasite that naturally does not form hypnozoites. Strikingly, individual expression of each protein in Py liver stages blocked liver stage schizogony, with parasites remaining small and uninucleate. A screen of RNA sequences that interact with the putative RNA-binding domains of these proteins showed enrichment of distinct, highly specific motifs, indicating that these protein might block schizogony by binding RNAs containing these motifs. Our findings provide the unprecedented functional evidence for one potential molecular mechanism of hypnozoite formation. Based on their function we named these proteins IESI-1 and IESI-2 (Initiation of Exo-erythrocytic Schizogony inhibited). Biological sciences/Cell biology/Mechanisms of disease Health sciences/Diseases/Infectious diseases/Malaria Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryTable1.xlsx Table S1 6.Sup.FigureFileReduced.pdf Figures S1-S5 SupplementaryFileX.xlsx Dataset 1 SupplementaryFileY.xlsx Dataset 2 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. 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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-8080228","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":547684917,"identity":"e0d034d5-7e65-4269-8e05-22cbbe187152","order_by":0,"name":"Stefan 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