Characterization of ovine A3Z1 restriction properties against small ruminant lentiviruses (SRLVs)
Date
2017Author
Version
Acceso abierto / Sarbide irekia
Type
Artículo / Artikulua
Version
Versión publicada / Argitaratu den bertsioa
Impact
|
10.3390/v9110345
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 t ...
[++]
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-
). 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. [--]
Subject
APOBEC3,
Small ruminant lentiviruses,
Restriction factors,
Deaminase domain,
Alternative splicing
Publisher
MDPI
Published in
Viruses, 2017, 9, 345
Departament
Universidad Pública de Navarra/Nafarroako Unibertsitate Publikoa. IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua
Publisher version
Sponsorship
Funded 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).