1177Iowa State University, Ames, IA, USA.
Veterinary Resources Inc, Cambridge, IA, USA.
Vet Pathol. 2021 Nov;58(6):1064-1074. doi: 10.1177/03009858211025794. Epub 2021 Oct 17.
Porcine astrovirus type 3 (PoAstV3) is an emerging virus in the family that has been recently associated with polioencephalomyelitis/encephalitis. Herein, we describe the experimental oral and intravenous inoculation of an infectious central nervous system (CNS) tissue homogenate containing PoAstV3 to cesarean-derived, colostrum-deprived pigs, and the subsequent development of clinical signs, histologic lesions, specific humoral immune response, and detection of viral particles by electron microscopy (EM) and viral RNA by RT-qPCR (reverse transcriptase quantitative polymerase chain reaction) and in situ hybridization (ISH). IgG against a portion of the PoAstV3 ORF2 capsid was first detected at 7 days post-inoculation (DPI) in 2 of 4 inoculated animals and in all inoculated animals by 14 DPI. At 21 and 28 DPI, 2 of 4 inoculated animals developed ataxia, tetraparesis, and/or lateral recumbency. All inoculated animals had histologic lesions in the CNS including perivascular lymphoplasmacytic cuffs, multifocal areas of gliosis with neuronal necrosis, satellitosis, and radiculoneuritis, and PoAstV3 RNA as detected by RT-qPCR within multiple anatomic regions of the CNS. Consistent viral structures were within the soma of a spinal cord neuron in the single pig examined by EM. Of note, PoAstV3 was not only detected by ISH in neurons of the cerebrum and spinal cord but also neurons of the dorsal root ganglion and nerve roots consistent with viral dissemination via axonal transport. This is the first study reproducing CNS disease with a porcine astrovirus strain consistent with natural infection, suggesting that pigs may serve as an animal model to study the pathogenesis of neurotropic astroviruses.
猪星状病毒 3 型(PoAstV3)是一种新兴的病毒家族成员,最近与脑脊髓灰质炎/脑炎有关。在此,我们描述了将含有 PoAstV3 的感染性中枢神经系统(CNS)组织匀浆通过口服和静脉途径接种给剖腹产、初乳缺乏的仔猪,以及随后发展的临床症状、组织病理学病变、特异性体液免疫反应、电镜(EM)检测病毒颗粒和 RT-qPCR(逆转录定量聚合酶链反应)及原位杂交(ISH)检测病毒 RNA。接种后 7 天(DPI),4 只接种动物中有 2 只首次检测到针对 PoAstV3 ORF2 衣壳的 IgG,14 DPI 时所有接种动物均检测到 IgG。21 和 28 DPI 时,4 只接种动物中有 2 只出现共济失调、四肢瘫痪和/或侧卧。所有接种动物的 CNS 均有组织病理学病变,包括血管周围淋巴浆细胞袖套、多灶性神经胶质增生伴神经元坏死、卫星现象和神经根炎,并且通过 RT-qPCR 在 CNS 的多个解剖区域检测到 PoAstV3 RNA。在通过 EM 检查的 1 只猪的单个脊髓神经元的胞体中发现了一致的病毒结构。值得注意的是,PoAstV3 通过 ISH 在大脑和脊髓神经元中以及背根神经节和神经根中的神经元中均被检测到,这与通过轴突运输进行病毒传播一致。这是首次使用与自然感染一致的猪星状病毒株复制 CNS 疾病的研究,表明猪可能作为研究神经嗜性星状病毒发病机制的动物模型。