Abstract
Small ruminant lentiviruses (SRLVs) are widely spread in the ovine and caprine populations, causing an incurable disease affecting animal health and production. Vaccine development is hindered owing to the high genetic heterogeneity of lentiviruses and the selection of T-cell and antibody escape mutants, requiring antigen delivery optimization. Sendai virus (SeV) is a respiratory paramyxovirus in mice that has been recognized as a potent inducer of innate immune responses in several species, including mouse and human. The aim of this study was to stimulate an innate antiviral response in ovine cells and evaluate the potential inhibitory effect upon small ruminant lentivirus (SRLV) infections. Ovine alveolar macrophages (AMs), blood-derived macrophages (BDMs), and skin fibroblasts (OSFs) were stimulated through infection with SeV encoding green fluorescent protein (GFP). SeV efficiently infected ovine cells, inducing an antiviral state in AM from SRLV naturally-infected animals, as well as in in vitro SRLV-infected BDM and OSF from non-infected animals. Supernatants from SeV-infected AM induced an antiviral state when transferred to fresh cells challenged with SRLV. Similar to SRLV, infectivity of an HIV-1-GFP lentiviral vector was also restricted in ovine cells infected with SeV. In myeloid cells, an M1-like proinflammatory polarization was observed together with an APOBEC3Z1 induction, among other lentiviral restriction factors. Our observations may boost new approximations in ameliorating the SRLV burden by stimulation of the innate immune response using SeV-based vaccine vectors.
Highlights
Small ruminant lentiviruses (SRLVs) are widely spread in sheep and goats throughout the world, causing a multiorgan disease affecting animal welfare and production
Vaccine-mediated immunization against Small Ruminant Lentivirus (SRLV) is ineffective in the same way as it remains elusive for other lentiviruses such as HIV [3]
Peripheral blood mononuclear cells (PBMCs) from SRLV-free sheep, confirmed by serology (EradikitTM SRLV, In3Diagnostic, Torino, Italy) and PCR [20,21], were seeded in 12-well plates and adherent cells were allowed to differentiate into blood-derived macrophages (BDMs) for twelve days of culture in Roswell Park Memorial Institute (RPMI) complete medium supplemented with 10% heat-inactivated fetal bovine serum (FBS) [22]
Summary
Small ruminant lentiviruses (SRLVs) are widely spread in sheep and goats throughout the world, causing a multiorgan disease affecting animal welfare and production. SRLV comprises Visna Maedi virus (VMV), the first lentivirus discovered and a good model for HIV studies Vaccine-mediated immunization against SRLV is ineffective in the same way as it remains elusive for other lentiviruses such as HIV [3]. Current control programs present some difficulties such as the ability to perform efficient and reliable serological tests to detect the complete antigenic spectrum that SRLV exhibits in nature, or the difficulty in detecting low antibody responders and delayed seroconversion [5,6]. SRLV can target and stably infect macrophages, controlling cellular response and modulating differentiation pathways and cytokine secretion in order to maintain a sustained replication [7,8]
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