Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, PR China; Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonose, Yangzhou University, Yangzhou, 225009, PR China.
Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, PR China.
Vet Microbiol. 2019 Aug;235:310-318. doi: 10.1016/j.vetmic.2019.07.024. Epub 2019 Jul 23.
Porcine reproductive and respiratory syndrome virus (PRRSV) causes great economic losses to the swine industry globally; however, effective control measures for this virus are limited. Here, we screened a porcine alveolar macrophage (PAM) cDNA library with a yeast two-hybrid system to reveal that galectin-1 (Gal-1), an endogenous innate immune protein encoded by LGALS1, interacts with nonstructural protein 11 (Nsp11) of PRRSV. Western blotting and viral titer assays indicated that Gal-1 overexpression suppressed replication in multiple PRRSV strains (P < 0.001), whereas Gal-1 knockdown or knockout increased viral titer and nucleocapsid protein expression. The Gal-1-specific anti-PRRSV effect was associated with the endoribonuclease domain of Nsp11 through inactivation of interferon-antagonist function and stimulation of interferon-stimulated gene expression. Additionally, Gal-1 interacted with PRRSV E protein but not with PRRSV glycoproteins, and recombinant Gal-1 treatment inhibited PRRSV in PAMs and MARC-145 cells. Furthermore, Gal-1 inhibited replication in multiple viruses, including equine arteritis virus, porcine epidemic diarrhea virus, pseudorabies virus, Japanese encephalitis virus, and classical swine fever virus, suggesting its potential broad application for antiviral strategies. Our findings provide insight into the important role of Gal-1 in PRRSV pathogenesis and its potential use as a novel therapeutic target against PRRSV infection.
猪繁殖与呼吸综合征病毒（PRRSV）在全球范围内给养猪业造成了巨大的经济损失；然而，目前针对该病毒的有效控制措施有限。在这里，我们使用酵母双杂交系统筛选了猪肺泡巨噬细胞（PAM）cDNA 文库，揭示了半乳糖凝集素-1（Gal-1），一种由 LGALS1 编码的内源性先天免疫蛋白，与 PRRSV 的非结构蛋白 11（Nsp11）相互作用。Western blot 和病毒滴度测定表明，Gal-1 过表达抑制了多种 PRRSV 株的复制（P<0.001），而 Gal-1 敲低或敲除则增加了病毒滴度和核衣壳蛋白表达。Gal-1 的抗 PRRSV 作用与 Nsp11 的内切核酸酶结构域有关，通过失活干扰素拮抗剂功能和刺激干扰素刺激基因表达。此外，Gal-1 与 PRRSV E 蛋白相互作用，但不与 PRRSV 糖蛋白相互作用，重组 Gal-1 处理抑制了 PAMs 和 MARC-145 细胞中的 PRRSV。此外，Gal-1 抑制了包括马动脉炎病毒、猪流行性腹泻病毒、猪伪狂犬病病毒、日本脑炎病毒和经典猪瘟病毒在内的多种病毒的复制，表明其在抗病毒策略中具有潜在的广泛应用。我们的研究结果揭示了 Gal-1 在 PRRSV 发病机制中的重要作用及其作为 PRRSV 感染新型治疗靶点的潜在用途。
