000152192 001__ 152192
000152192 005__ 20250401114419.0
000152192 0247_ $$2doi$$a10.1186/s13567-025-01475-2
000152192 0248_ $$2sideral$$a143426
000152192 037__ $$aART-2025-143426
000152192 041__ $$aeng
000152192 100__ $$aGómez, Álex$$uUniversidad de Zaragoza
000152192 245__ $$aCharacterization of a recombinant Sendai virus vector encoding the small ruminant lentivirus gag-P25: antiviral properties in vitro and transgene expression in sheep
000152192 260__ $$c2025
000152192 5060_ $$aAccess copy available to the general public$$fUnrestricted
000152192 5203_ $$aAbstract
          Small ruminant lentiviruses (SRLV) cause multisystemic chronic inflammatory disease and significant economic losses in sheep and goats worldwide. However, no vaccines or therapies are currently available. In this study, a recombinant Sendai virus (SeV) vector encoding the SRLV gag-P25 gene (rSeV-GFP-P25) from the EV1 strain was generated using In-FUSION cloning and rescued using the SeV reverse genetic system. Transgene expression and stimulation of innate immunity and interferon-stimulated genes (ovine A3Z1, OBST2 and SAMHD1) were evaluated in ovine skin fibroblasts (OSF) transduced with SeV-GFP and rSeV-GFP-P25. Additionally, to characterize the effect of the SRLV restriction in transduced OSF, the SRLV DNA load was quantified at different times post-transduction and post-infection with strain EV1. Using immunohistochemistry and image analysis, transgene expression and tissue distribution of recombinant P25 were studied in two lambs inoculated intranasally, one with rSeV-GFP-P25 and the other with SeV-GFP. rSeV-GFP-P25 induced efficient and transient transgene expression in vitro and in vivo. Furthermore, OSF transduced with rSeV-GFP-P25 presented upregulation of TLR2, TLR3, TLR6, TLR7, RIG-I, MyD88 and IFN-β, whereas SeV-GFP did not induce TLR6 or IFN-β upregulation. Among the interferon-stimulated genes, OBST2 was significantly upregulated after transduction with rSeV-GFP-P25 compared with the empty vector. SRLV restriction gradually increased and persisted after transduction with SeV-GFP and rSeV-GFP-P25, with OSF transduced three times showing cumulative restriction. Forty-eight hours post-inoculation in vivo, marked P25 expression was observed in ciliated epithelial cells and submucosal macrophages/dendritic cells of the nasal mucosa. This study reinforces the important role of the innate immune response in controlling SRLV infection and suggests that rSeV-GFP-P25 is a potential vaccine candidate against SRLV.
000152192 536__ $$9info:eu-repo/grantAgreement/ES/MCIU/RTI2018-096172-B-C33
000152192 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000152192 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000152192 700__ $$aGlaria, Idoia
000152192 700__ $$aMoncayola, Irati
000152192 700__ $$aEcheverría, Irache
000152192 700__ $$aArrizabalaga, Javier
000152192 700__ $$0(orcid)0000-0002-2685-1730$$aRodríguez-Largo, Ana
000152192 700__ $$0(orcid)0000-0002-1204-4356$$ade Blas, Ignacio$$uUniversidad de Zaragoza
000152192 700__ $$0(orcid)0000-0002-7822-6646$$aLacasta, Delia$$uUniversidad de Zaragoza
000152192 700__ $$aPérez, Estela$$uUniversidad de Zaragoza
000152192 700__ $$0(orcid)0000-0002-8133-2124$$aPérez, Marta$$uUniversidad de Zaragoza
000152192 700__ $$aDe Diego, Alicia
000152192 700__ $$aDe-Miguel, Ricardo
000152192 700__ $$aLee, Benhur
000152192 700__ $$0(orcid)0000-0002-2053-9842$$aLuján, Lluís$$uUniversidad de Zaragoza
000152192 700__ $$aReina, Ramsés
000152192 7102_ $$12009$$2750$$aUniversidad de Zaragoza$$bDpto. Química Analítica$$cÁrea Química Analítica
000152192 7102_ $$11009$$2773$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Sanidad Animal
000152192 7102_ $$11001$$2025$$aUniversidad de Zaragoza$$bDpto. Anatom.,Embri.Genét.Ani.$$cÁrea Anatom.Anatom.Patológ.Com
000152192 7102_ $$11009$$2617$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Medicina y Cirugía Animal
000152192 773__ $$g56, 51 (2025), [14 pp.]$$pVet. res.$$tVeterinary Research$$x0928-4249
000152192 8564_ $$s3323273$$uhttps://zaguan.unizar.es/record/152192/files/texto_completo.pdf$$yVersión publicada
000152192 8564_ $$s2230220$$uhttps://zaguan.unizar.es/record/152192/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000152192 909CO $$ooai:zaguan.unizar.es:152192$$particulos$$pdriver
000152192 951__ $$a2025-04-01-11:02:28
000152192 980__ $$aARTICLE