HTLV-1 subverts the innate immune effector gene IRF7 by viral HBZ protein for oncogenesis

HTLV-1 subverts the innate immune effector gene IRF7 by viral HBZ protein for oncogenesis | 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 HTLV-1 subverts the innate immune effector gene IRF7 by viral HBZ protein for oncogenesis Guangyong Ma, Xiaoyi Yuan, Yunyun Yue, Liang Chen, Dongmei Liu, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7587883/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 Interferon regulatory factors (IRFs) are innate immune transcription factors responsible for inducing the expression of type I interferons (IFN-I), which combat pathogen invasions via initiating the downstream Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway. Among them, IRF7 plays a central role by forming heterodimers with IRF3 to initiate IFN-I production and is therefore frequently targeted by viruses to evade immune detection. Contrary to this common paradigm, we show that IRF7 is activated and upregulated by the retrovirus human T-cell leukemia virus type 1 (HTLV-1), via its oncoprotein HBZ. Moreover, IRF7 is highly expressed in HTLV-1 induced CD4 T-cell malignancy named adult T-cell leukemia/lymphoma (ATLL), and promotes the proliferation of infected cells both in vitro and in vivo. Intriguingly, HBZ is able to interfere with the interaction of IRF7 and IRF3, likely accounting for the inactive IFN-I pathway in ATLL cells. Unexpectedly, IRF7 was found to directly upregulate the transcription of STAT5B, a transcription factor of the JAK-STAT pathway frequently mutated in hematological malignancies. Together, these findings reveal a novel mechanism by which HTLV-1 hijacks a critical innate immune effector to sustain persistent infection and drive oncogenesis without activating antiviral IFN-I pathway. Biological sciences/Microbiology/Virology/HTLV Health sciences/Oncology/Cancer/Tumour virus infections IRF7 STAT5B Oncogene Leukemia HTLV-1 HBZ Zebrafish Full Text Additional Declarations There is NO Competing Interest. Supplementary Files nrreportingsummary20251023.pdf Reporting Summary 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-7587883","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":539918084,"identity":"028d413d-ca99-4f45-841e-41dc9b2d8b92","order_by":0,"name":"Guangyong 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