Pablo-Maiso Lorena de, Echeverría Irache, Rius-Rocabert Sergio, Luján Lluís, Garcin Dominique, Andrés Damián de, Nistal-Villán Estanislao, Reina Ramsés
Department of Animal Health, Institute of Agrobiotechnology (CSIC-Government of Navarra), 31192 Mutilva, Navarra, Spain.
Microbiology Section, Departamento Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU San Pablo, CEU Universities, Boadilla del Monte, 28668 Madrid, Spain.
Vaccines (Basel). 2020 Apr 29;8(2):206. doi: 10.3390/vaccines8020206.
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 SRLVinfected 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.
小反刍兽慢病毒（SRLVs）在绵羊和山羊群体中广泛传播，引发一种影响动物健康和生产且无法治愈的疾病。由于慢病毒的高遗传异质性以及T细胞和抗体逃逸突变体的选择，疫苗研发受到阻碍，这就需要优化抗原递送。仙台病毒（SeV）是小鼠中的一种呼吸道副粘病毒，已被公认为包括小鼠和人类在内的多个物种中先天免疫反应的有效诱导剂。本研究的目的是在绵羊细胞中激发先天抗病毒反应，并评估其对小反刍兽慢病毒（SRLV）感染的潜在抑制作用。通过感染编码绿色荧光蛋白（GFP）的SeV来刺激绵羊肺泡巨噬细胞（AMs）、血液来源的巨噬细胞（BDMs）和皮肤成纤维细胞（OSFs）。SeV有效感染绵羊细胞，在来自SRLV自然感染动物的AMs以及来自未感染动物的体外SRLV感染的BDM和OSF中诱导抗病毒状态。当将SeV感染的AMs的上清液转移到受SRLV攻击的新鲜细胞中时，会诱导抗病毒状态。与SRLV类似，HIV-1-GFP慢病毒载体的感染性在感染SeV的绵羊细胞中也受到限制。在髓样细胞中，观察到类似M1的促炎极化以及APOBEC3Z1诱导，以及其他慢病毒限制因子。我们的观察结果可能会推动通过使用基于SeV的疫苗载体刺激先天免疫反应来减轻SRLV负担的新方法。
