Characterization of ovine A3Z1 restriction properties against small ruminant lentiviruses (SRLVs)

dc.contributor.authorPablo Maiso, Lorena de
dc.contributor.authorGlaría Ezquer, Idoia
dc.contributor.authorCrespo Otano, Helena
dc.contributor.authorNistal Villán, Estanislao
dc.contributor.authorAndrésdóttir, Valgerdur
dc.contributor.authorAndrés Cara, Damián de
dc.contributor.authorAmorena Zabalza, Beatriz
dc.contributor.authorReina Arias, Ramsés
dc.contributor.departmentIdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutuaes_ES
dc.contributor.funderGobierno de Navarra / Nafarroako Gobernuaes
dc.contributor.funderUniversidad Pública de Navarra / Nafarroako Unibertsitate Publikoaen
dc.date.accessioned2018-10-02T07:58:01Z
dc.date.available2018-10-02T07:58:01Z
dc.date.issued2017
dc.description.abstractIntrinsic factors of the innate immune system include the apolipoprotein B editing enzyme catalytic polypeptide-like 3 (APOBEC3) protein family. APOBEC3 inhibits replication of different virus families by cytosine deamination of viral DNA and a not fully characterized cytosine deamination-independent mechanism. Sheep are susceptible to small ruminant lentivirus (SRLVs) infection and contain three APOBEC3 genes encoding four proteins (A3Z1, Z2, Z3 and Z2-Z3) with yet not deeply described antiviral properties. Using sheep blood monocytes and in vitro-derived macrophages, we found that A3Z1 expression is associated with lower viral replication in this cellular type. A3Z1 transcripts may also contain spliced variants (A3Z1Tr) lacking the cytidine deaminase motif. A3Z1 exogenous expression in fully permissive fibroblast-like cells restricted SRLVs infection while A3Z1Tr allowed infection. A3Z1Tr was induced after SRLVs infection or stimulation of blood-derived macrophages with interferon gamma (IFN- ). Interaction between truncated isoform and native A3Z1 protein was detected as well as incorporation of both proteins into virions. A3Z1 and A3Z1Tr interacted with SRLVs Vif, but this interaction was not associated with degradative properties. Similar A3Z1 truncated isoforms were also present in human and monkey cells suggesting a conserved alternative splicing regulation in primates. A3Z1-mediated retroviral restriction could be constrained by different means, including gene expression and specific alternative splicing regulation, leading to truncated protein isoforms lacking a cytidine-deaminase motif.en
dc.description.sponsorshipFunded by CICYT (AGL2010-22341-C04-01) and Navarra’s Government (IIQ010449.RI1, IIQ14064.RI1 and PI042-LENTIMOL). Ramsés Reina was supported by the Spanish Ministry of Science and Innovation “Ramón y Cajal” contract. The authors acknowledge support of the publication fee by the Public University of Navarra and CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).en
dc.format.extent19 p.
dc.format.mimetypeapplication/pdfen
dc.identifier.doi10.3390/v9110345
dc.identifier.issn1999-4915
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/30883
dc.language.isoengen
dc.publisherMDPIen
dc.relation.ispartofViruses, 2017, 9, 345en
dc.relation.publisherversionhttps://doi.org/10.3390/v9110345
dc.rights© 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.en
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAPOBEC3en
dc.subjectSmall ruminant lentivirusesen
dc.subjectRestriction factorsen
dc.subjectDeaminase domainen
dc.subjectAlternative splicingen
dc.titleCharacterization of ovine A3Z1 restriction properties against small ruminant lentiviruses (SRLVs)en
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
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relation.isAuthorOfPublicationb8d67008-109a-45c4-b632-218257bb3511
relation.isAuthorOfPublicatione28c17f3-459d-4b77-9d08-2c325e7150da
relation.isAuthorOfPublication50c83dcd-b739-4348-b0f0-3a230e16c398
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relation.isAuthorOfPublication.latestForDiscovery507ffb8b-ec19-4f04-aa65-df6463910dcb

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