Dynamics of antiretroviral restriction factor expression in sheep naturally infected with Small Ruminant Lentivirus (SRLV).

Dynamics of antiretroviral restriction factor expression in sheep naturally infected with Small Ruminant Lentivirus (SRLV). | 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 Research Article Dynamics of antiretroviral restriction factor expression in sheep naturally infected with Small Ruminant Lentivirus (SRLV). Cecilia Rodriguez-Murillo, Víctor David González-Fernández, Gabriela Castillo-Hernández, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7992658/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 26 Feb, 2026 Read the published version in Archives of Virology → Version 1 posted 5 You are reading this latest preprint version Abstract Small Ruminant Lentiviruses (SRLV) cause persistent, slowly progressive infections in sheep and goats, characterized by high genetic variability and a fluctuating immune response that hinders accurate diagnosis and, consequently, effective control. In this study, we monitored the dynamics of SRLV infection and the expression of antiretroviral restriction factors in a flock of 47 ewes over a 16-month period. Six serial samplings were conducted to assess antibodies detection, cell-associated viral load, proviral load, and gene expression of the APOBEC3 Z1, Z3, and tetherin proteins using absolute quantification qPCR. Tetherin expression was consistently observed across most animals and sampling points, whereas APOBEC3 Z1 and Z3 showed intermittent patterns. Statistical analyses revealed significant correlations between gene expression levels and both viral and proviral loads, highlighting distinct role of each factor in the SRLV infection dynamics. Notably, viral RNA was frequently detected, even when provirus or antibodies were absent. These results underscore the involvement of the innate immune response and highlight the potential role of restriction factors as modulators of SRLV infection under natural conditions. SRLV Antiretroviral restriction factors APOBEC3 Tetherin Proviral load Bayesian modeling Figures Figure 1 Figure 2 Figure 3 Figure 4 Full Text Additional Declarations Table 1 is available in the Supplementary Files section. Supplementary Files Table1.docx SupplementarydataV2.docx Cite Share Download PDF Status: Published Journal Publication published 26 Feb, 2026 Read the published version in Archives of Virology → Version 1 posted Editorial decision: Major Revision 05 Dec, 2025 Reviewers agreed at journal 10 Nov, 2025 Reviewers invited by journal 06 Nov, 2025 Editor assigned by journal 03 Nov, 2025 First submitted to journal 30 Oct, 2025 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. 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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-7992658","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":541026743,"identity":"f8da817e-7cf8-4f0d-b252-280fcb5a36e9","order_by":0,"name":"Cecilia Rodriguez-Murillo","email":"","orcid":"","institution":"UNAM FESC: Universidad Nacional Autonoma de Mexico Facultad de Estudios Superiores Cuautitlan","correspondingAuthor":false,"prefix":"","firstName":"Cecilia","middleName":"","lastName":"Rodriguez-Murillo","suffix":""},{"id":541026744,"identity":"8c87a98f-1670-41cd-a231-3e8b199ad4d3","order_by":1,"name":"Víctor David 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05:02:45","extension":"html","order_by":20,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":141810,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7992658/v1/df38d07894a085653d2159d3.html"},{"id":96139578,"identity":"f51ecb5f-cba3-44a2-977f-d3bfe9702c45","added_by":"auto","created_at":"2025-11-18 05:02:45","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":86964,"visible":true,"origin":"","legend":"\u003cp\u003eSerological dynamics of SRLV infection across six sampling points Serological status was assessed using an indirect ELISA targeting the recombinant capsid protein p25 from SRLV genotype B1. All animals (n = 47) were tested at each of the six sampling points. The X-axis represents the sampling points (1 to 6), while the Y-axis shows the number of seropositive (solid line with circles) and seronegative (dashed line with squares) animals. A progressive increase in the number of seropositive animals was observed over time, reaching a peak at sampling point 5. Cases of seroreversion were also detected, in which some previously seropositive animals became seronegative in later samplings.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7992658/v1/66d7e3c6b40b93fde6605c58.png"},{"id":96139577,"identity":"900f5a02-7e47-4f17-941a-031b57fe3a6b","added_by":"auto","created_at":"2025-11-18 05:02:45","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":303726,"visible":true,"origin":"","legend":"\u003cp\u003eHeatmap of proviral and viral loads in sheep over time Heatmap displaying proviral load (left panel) and cell-associated viral load (right panel) in peripheral blood samples from 47 sheep over six sampling points during a 16-month follow-up. Each row represents an individual animal, and each column represents a time point. Data are shown as row Z-scores of absolute quantification values (copies/ng DNA), with green indicating higher expression levels. This visualization highlights the dynamic nature of SRLV infection: in early sampling points, viral RNA is detected more frequently and at higher levels, suggesting active replication. In contrast, towards the final sampling points, proviral DNA becomes more prevalent, indicating viral integration and reduced replication, a pattern consistent with progression toward viral latency and chronic infection. These findings support the notion that time is a critical factor in shaping the dynamics of infection.\u003c/p\u003e","description":"","filename":"Figure2V1.png","url":"https://assets-eu.researchsquare.com/files/rs-7992658/v1/eaba2b484c0beacac6b2a7b9.png"},{"id":96139587,"identity":"1f8a7b72-a590-45d3-baa2-7dc6eb30c66e","added_by":"auto","created_at":"2025-11-18 05:02:45","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":411265,"visible":true,"origin":"","legend":"\u003cp\u003eExpression heatmap of restriction factors during SRLV infection. Heatmap displaying the absolute gene expression (row Z-scores) of APOBEC3 Z1, APOBEC3 Z3, and Tetherin (BST2) in peripheral blood leukocytes from 47 sheep across six sampling points during a 16-month SRLV follow-up. Each row represents an individual animal, and each column a time point. While Z1 showed sporadic and low-level expression, Z3 was more frequently detected with variable intensity, and Tetherin exhibited consistent, high expression across most animals and time points. This pattern suggests distinct regulatory dynamics and potentially complementary antiviral roles during infection.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-7992658/v1/c04d909409f273afe6427180.png"},{"id":96139581,"identity":"d7277bbe-1fed-4df0-8a23-6e9e7830a20f","added_by":"auto","created_at":"2025-11-18 05:02:45","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":346199,"visible":true,"origin":"","legend":"\u003cp\u003eBayesian regression model estimates for the impact of restriction factor expression and time on viral and proviral loads. Posterior estimates from Bayesian lognormal regression models evaluating the effect of APOBEC3 Z1, APOBEC3 Z3, BST2/Tetherin, and sampling time on viral load (top panel) and proviral load (bottom panel). Points represent posterior means of the estimated regression coefficients (β), and bars denote the 95% credible intervals. APOBEC3 Z1 showed a positive association with viral load, while APOBEC3 Z3 was negatively associated with viral load but positively associated with proviral load.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-7992658/v1/14c714c276553754f7fcac77.png"},{"id":103766182,"identity":"84fe2dc3-0b34-44ef-8271-ffba9a3534b0","added_by":"auto","created_at":"2026-03-02 16:12:54","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":738331,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptRodriguezetal.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7992658/v1_covered_a279e5f6-3cbe-42a5-b1cd-272c5302e14e.pdf"},{"id":96139579,"identity":"276eabdf-6608-4634-a481-916ea73eb8cd","added_by":"auto","created_at":"2025-11-18 05:02:45","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":16986,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-7992658/v1/ec7ad651ba072637b8bdc0d2.docx"},{"id":96139593,"identity":"44d1479a-6d73-4582-8869-939afaf1670b","added_by":"auto","created_at":"2025-11-18 05:02:45","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":600978,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementarydataV2.docx","url":"https://assets-eu.researchsquare.com/files/rs-7992658/v1/1008df97f71bb0b9a568a626.docx"}],"financialInterests":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e","formattedTitle":"Dynamics of antiretroviral restriction factor expression in sheep naturally infected with Small Ruminant Lentivirus (SRLV).","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"archives-of-virology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arvi","sideBox":"Learn more about [Archives of Virology](https://www.springer.com/journal/705)","snPcode":"705","submissionUrl":"https://submission.nature.com/new-submission/705/3","title":"Archives of Virology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"SRLV, Antiretroviral restriction factors, APOBEC3, Tetherin, Proviral load, Bayesian modeling","lastPublishedDoi":"10.21203/rs.3.rs-7992658/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7992658/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cem\u003eSmall Ruminant Lentiviruses\u003c/em\u003e (SRLV) cause persistent, slowly progressive infections in sheep and goats, characterized by high genetic variability and a fluctuating immune response that hinders accurate diagnosis and, consequently, effective control. In this study, we monitored the dynamics of SRLV infection and the expression of antiretroviral restriction factors in a flock of 47 ewes over a 16-month period. Six serial samplings were conducted to assess antibodies detection, cell-associated viral load, proviral load, and gene expression of the APOBEC3 Z1, Z3, and tetherin proteins using absolute quantification qPCR. Tetherin expression was consistently observed across most animals and sampling points, whereas APOBEC3 Z1 and Z3 showed intermittent patterns. Statistical analyses revealed significant correlations between gene expression levels and both viral and proviral loads, highlighting distinct role of each factor in the SRLV infection dynamics. Notably, viral RNA was frequently detected, even when provirus or antibodies were absent. These results underscore the involvement of the innate immune response and highlight the potential role of restriction factors as modulators of SRLV infection under natural conditions.\u003c/p\u003e","manuscriptTitle":"Dynamics of antiretroviral restriction factor expression in sheep naturally infected with Small Ruminant Lentivirus (SRLV).","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-18 05:02:40","doi":"10.21203/rs.3.rs-7992658/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major Revision","date":"2025-12-06T01:36:59+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-11-10T06:17:54+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-06T13:45:06+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-03T07:44:59+00:00","index":"","fulltext":""},{"type":"submitted","content":"Archives of Virology","date":"2025-10-30T17:07:46+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"archives-of-virology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arvi","sideBox":"Learn more about [Archives of Virology](https://www.springer.com/journal/705)","snPcode":"705","submissionUrl":"https://submission.nature.com/new-submission/705/3","title":"Archives of Virology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"3a243ce3-b648-477e-84ef-f7f3b1297d4f","owner":[],"postedDate":"November 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-02T16:09:54+00:00","versionOfRecord":{"articleIdentity":"rs-7992658","link":"https://doi.org/10.1007/s00705-026-06587-4","journal":{"identity":"archives-of-virology","isVorOnly":false,"title":"Archives of Virology"},"publishedOn":"2026-02-26 15:57:48","publishedOnDateReadable":"February 26th, 2026"},"versionCreatedAt":"2025-11-18 05:02:40","video":"","vorDoi":"10.1007/s00705-026-06587-4","vorDoiUrl":"https://doi.org/10.1007/s00705-026-06587-4","workflowStages":[]},"version":"v1","identity":"rs-7992658","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7992658","identity":"rs-7992658","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}