Inhibition of the signal peptidase complex blocks cleavage of HTLV-1 ORF-I encoded p12 to p8 and impairs virus transmission

Inhibition of the signal peptidase complex blocks cleavage of HTLV-1 ORF-I encoded p12 to p8 and impairs virus transmission | 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 Inhibition of the signal peptidase complex blocks cleavage of HTLV-1 ORF-I encoded p12 to p8 and impairs virus transmission Andrea Thoma-Kress, Florian Simon, Norbert Donhauser, Laura Kemeter, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6064775/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Infection with the oncogenic delta-retrovirus Human T-cell Leukemia Virus Type 1 (HTLV-1) causes aggressive CD4+ T-cell malignancy or progressive neuroinflammatory disorders. The HTLV-1 accessory protein p8 is important for viral persistence and induces formation of cellular conduits, thereby enhancing HTLV-1 cell-to-cell transmission. p8 is a cleavage product of its precursor protein p12. To date, host factors cleaving p12 to p8 remain unknown impeding delineation of functions of p12 from those of p8. Here, we report that p12 carries a signal peptide (SP) that is cleaved by the signal peptidase complex (SPC) to generate p8. SPC-inhibition blocked p12 cleavage, impaired conduit formation and cell-to-cell transmission. Based on these findings, computational predictions allowed us to generate cleavage-deficient p12 mutants. Thus, we identified the host cell factors cleaving p12 to p8 harboring the potential to lower the viral burden and to study the functions of p12 and p8 independently of each other. Biological sciences/Microbiology/Virology/HTLV Biological sciences/Microbiology/Virology/Retrovirus Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SimonetalSupplementaryFile.pdf Supplementary Figures Simon et al. Cite Share Download PDF Status: Posted 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-6064775","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":425263307,"identity":"f650181e-05c2-4510-ab4c-fd945c90cb0d","order_by":0,"name":"Andrea 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