Neuropathogenicity of Two Saffold Virus Type 3 Isolates in Mouse Models

ObjectiveSaffold virus (SAFV), a picornavirus, is occasionally detected in children with acute flaccid paralysis, meningitis, and cerebellitis; however, the neuropathogenicity of SAFV remains undetermined.MethodsThe virulence of two clinical isolates of SAFV type 3 (SAFV-3) obtained from a patient with aseptic meningitis (AM strain) and acute upper respiratory inflammation (UR strain) was analyzed in neonatal and young mice utilizing virological, pathological, and immunological methods.ResultsThe polyproteins of the strains differed in eight amino acids. Both clinical isolates were infective, exhibited neurotropism, and were mildly neurovirulent in neonatal ddY mice. Both strains pathologically infected neural progenitor cells and glial cells, but not large neurons, with the UR strain also infecting epithelial cells. UR infection resulted in longer inflammation in the brain and spinal cord because of demyelination, while the AM strain showed more infectivity in the cerebellum in neonatal ddY mice. Additionally, young BALB/c mice seroconverted following mucosal inoculation with the UR, but not the AM, strain.ConclusionsBoth SAFV-3 isolates had neurotropism and mild neurovirulence but showed different cell tropisms in both neonatal and young mouse models. This animal model has the potential to recapitulate the potential neuropathogenicity of SAFV-3.研究目的：Saffold病毒（Saffold virus, SAFV）属于小核糖核酸病毒（picornavirus），偶尔可在罹患急性弛缓性麻痹、脑膜炎及小脑炎的儿童样本中检出，但SAFV的神经致病性仍未明确。 方法：本研究利用病毒学、病理学及免疫学方法，在新生及幼年小鼠体内分析了两株3型SAFV（SAFV-3）临床分离株的毒力，两株分离株分别分离自一名无菌性脑膜炎患者（AM株）与一名急性上呼吸道炎症患者（UR株）。 结果：两株分离株的多聚蛋白存在8个氨基酸差异。两株临床分离株均具有感染性，表现出嗜神经性，且在新生ddY小鼠中呈现轻度神经毒力。二者均可病理性感染神经祖细胞与胶质细胞，但无法感染大型神经元；其中UR株还可感染上皮细胞。UR株感染可因脱髓鞘导致脑与脊髓的炎症持续时间更长，而AM株在新生ddY小鼠的小脑组织中感染性更强。此外，幼年BALB/c小鼠经黏膜接种UR株后可发生血清阳转，接种AM株则未出现该现象。 结论：两株SAFV-3分离株均具有嗜神经性与轻度神经毒力，但在新生及幼年小鼠模型中展现出不同的细胞嗜性。本动物模型有望复现SAFV-3潜在的神经致病性。