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Viruses. 2017 Nov 17;9(11). pii: E345. doi: 10.3390/v9110345.

Characterization of Ovine A3Z1 Restriction Properties against Small Ruminant Lentiviruses (SRLVs).

Author information

1
Instituto de Agrobiotecnología, UPNA-CSIC-Gobierno de Navarra, 31192 Mutilva, Spain. lorena.depablo@unavarra.es.
2
Instituto de Agrobiotecnología, UPNA-CSIC-Gobierno de Navarra, 31192 Mutilva, Spain. idoia.g@unavarra.es.
3
Instituto de Agrobiotecnología, UPNA-CSIC-Gobierno de Navarra, 31192 Mutilva, Spain. helena.crespo@unavarra.es.
4
Sección 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, Spain. estanislao.nistalvillan@ceu.es.
5
Institute for Experimental Pathology, University of Iceland, Keldur, 112 Reykjavik, Iceland. valand@hi.is.
6
Instituto de Agrobiotecnología, UPNA-CSIC-Gobierno de Navarra, 31192 Mutilva, Spain. ancad@unavarra.es.
7
Instituto de Agrobiotecnología, UPNA-CSIC-Gobierno de Navarra, 31192 Mutilva, Spain. bamorena@unavarra.es.
8
Instituto de Agrobiotecnología, UPNA-CSIC-Gobierno de Navarra, 31192 Mutilva, Spain. ramses.reina@unavarra.es.

Abstract

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.

KEYWORDS:

APOBEC3; alternative splicing; deaminase domain; restriction factors; small ruminant lentiviruses

PMID:
29149056
PMCID:
PMC5707552
DOI:
10.3390/v9110345
[Indexed for MEDLINE]
Free PMC Article

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