CYP1B1-AS1 regulates CYP1B1 to promote Coxiella burnetii pathogenesis by inhibiting ROS and host cell death.

CYP1B1-AS1 regulates CYP1B1 to promote Coxiella burnetii pathogenesis by inhibiting ROS and host cell death. | 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 CYP1B1-AS1 regulates CYP1B1 to promote Coxiella burnetii pathogenesis by inhibiting ROS and host cell death. James Samuel, Aryashree Arunima, Seyednami Niyakan, Samantha Butler, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5390645/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 Coxiella burnetii (Cb), the causative agent of Q fever, replicates within host macrophages by modulating immune responses through poorly understood mechanisms. Long non-coding RNAs (lncRNAs) are emerging as critical regulators of inflammation, yet their role in Cb pathogenesis remains largely unexplored. Here, we employed a global transcriptomic approach to identify lncRNAs specific to Cb infection in THP-1 derived macrophages, compared to 15 other microbial infections. CYP1B1-AS1 was uniquely regulated in a spatio-temporal manner during Cb infection. Promoter assays revealed that CYP1B1-AS1 is transcribed by AHR from a bidirectional promoter, enhancing CYP1B1 expression in cis. Inhibition of CYP1B1-AS1 and CYP1B1 increased reactive oxygen species (ROS), mitochondrial membrane depolarization, and apoptosis, suggesting their role in dampening host cell death. Additionally, immunoprecipitation followed by mass spectrometry identified the mitochondrially localized Cb effector CBU_0937 as an interactor of the CYP1B1 enzyme. These events facilitate Cb intracellular survival. Our findings identify CYP1B1-AS1 as a potential molecular target for combating Cb infection. Biological sciences/Microbiology/Pathogens Biological sciences/Cell biology/Mechanisms of disease Coxiella burnetii CYP1B1-AS1 lncRNA marker CYP1B1 reactive oxygen species (ROS) apoptosis inflammation bacterial pathogenesis mitochondrial effector CBU_0937 Full Text Additional Declarations There is NO Competing Interest. Animal ethics statement Male and female C57BL/6 mice (6–8 weeks old, n=5) were purchased from Envigo Laboratories and acclimatized in pathogen-free isolator cages with ad libitum access to food and water. The animal study was reviewed and approved by the Institute of Animal Care and Use Committee (IACUC) (IACUC 2020-0310D) at Texas A&M University. Experiments were conducted in an Animal-BSL3 (ABSL3) facility in accordance with IACUC guidelines and federal regulations. Supplementary Files SupplementalPDFArunimaetal2024.pdf CYP1B1-AS1 regulates CYP1B1 to promote Coxiella burnetii pathogenesis by inhibiting ROS and host cell death. datasets.zip Dataset S1 to Dataset S9 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. 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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-5390645","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":382307436,"identity":"08327ab0-a782-440e-bd35-ddff95000b07","order_by":0,"name":"James 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