Characterization of Ovine A3Z1 Restriction Properties against Small Ruminant Lentiviruses (SRLVs)
Intrinsic 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-independen...
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| Language: | English |
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MDPI AG
2017-11-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/9/11/345 |
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| author | Lorena de Pablo-Maiso Idoia Glaria Helena Crespo Estanislao Nistal-Villán Valgerdur Andrésdóttir Damián de Andrés Beatriz Amorena Ramsés Reina |
| author_facet | Lorena de Pablo-Maiso Idoia Glaria Helena Crespo Estanislao Nistal-Villán Valgerdur Andrésdóttir Damián de Andrés Beatriz Amorena Ramsés Reina |
| author_sort | Lorena de Pablo-Maiso |
| collection | DOAJ |
| description | Intrinsic 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-γ). 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. |
| first_indexed | 2024-04-13T19:37:34Z |
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| id | doaj.art-234b322deb6844739a15261d84b90b54 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-04-13T19:37:34Z |
| publishDate | 2017-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-234b322deb6844739a15261d84b90b542022-12-22T02:32:58ZengMDPI AGViruses1999-49152017-11-0191134510.3390/v9110345v9110345Characterization of Ovine A3Z1 Restriction Properties against Small Ruminant Lentiviruses (SRLVs)Lorena de Pablo-Maiso0Idoia Glaria1Helena Crespo2Estanislao Nistal-Villán3Valgerdur Andrésdóttir4Damián de Andrés5Beatriz Amorena6Ramsés Reina7Instituto de Agrobiotecnología, UPNA-CSIC-Gobierno de Navarra, 31192 Mutilva, SpainInstituto de Agrobiotecnología, UPNA-CSIC-Gobierno de Navarra, 31192 Mutilva, SpainInstituto de Agrobiotecnología, UPNA-CSIC-Gobierno de Navarra, 31192 Mutilva, SpainSección de Microbiología, Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo C.E.U. Ctra, Boadilla del Monte Km, 28003 Madrid, SpainInstitute for Experimental Pathology, University of Iceland, Keldur, 112 Reykjavik, IcelandInstituto de Agrobiotecnología, UPNA-CSIC-Gobierno de Navarra, 31192 Mutilva, SpainInstituto de Agrobiotecnología, UPNA-CSIC-Gobierno de Navarra, 31192 Mutilva, SpainInstituto de Agrobiotecnología, UPNA-CSIC-Gobierno de Navarra, 31192 Mutilva, SpainIntrinsic 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-γ). 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.https://www.mdpi.com/1999-4915/9/11/345APOBEC3small ruminant lentivirusesrestriction factorsdeaminase domainalternative splicing |
| spellingShingle | Lorena de Pablo-Maiso Idoia Glaria Helena Crespo Estanislao Nistal-Villán Valgerdur Andrésdóttir Damián de Andrés Beatriz Amorena Ramsés Reina Characterization of Ovine A3Z1 Restriction Properties against Small Ruminant Lentiviruses (SRLVs) Viruses APOBEC3 small ruminant lentiviruses restriction factors deaminase domain alternative splicing |
| title | Characterization of Ovine A3Z1 Restriction Properties against Small Ruminant Lentiviruses (SRLVs) |
| title_full | Characterization of Ovine A3Z1 Restriction Properties against Small Ruminant Lentiviruses (SRLVs) |
| title_fullStr | Characterization of Ovine A3Z1 Restriction Properties against Small Ruminant Lentiviruses (SRLVs) |
| title_full_unstemmed | Characterization of Ovine A3Z1 Restriction Properties against Small Ruminant Lentiviruses (SRLVs) |
| title_short | Characterization of Ovine A3Z1 Restriction Properties against Small Ruminant Lentiviruses (SRLVs) |
| title_sort | characterization of ovine a3z1 restriction properties against small ruminant lentiviruses srlvs |
| topic | APOBEC3 small ruminant lentiviruses restriction factors deaminase domain alternative splicing |
| url | https://www.mdpi.com/1999-4915/9/11/345 |
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