The Role of Coronavirus Spike Protein in Inducing Optic Neuritis in Mice: Parallels to the SARS-CoV-2 Virus.

IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Journal of Neuro-Ophthalmology Pub Date : 2024-09-01 DOI:10.1097/WNO.0000000000002234
Grishma Kasle, Jayasri Das Sarma
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Abstract

Background: Optic neuritis (ON), one of the clinical manifestations of the human neurological disease multiple sclerosis (MS), was also reported in patients with COVID-19 infection, highlighting one potential neurological manifestation of SARS-CoV-2. However, the mechanism of ON in these patients is poorly understood.

Evidence acquisition: Insight may be gained by studying the neurotropic mouse hepatitis virus (MHV-A59), a β-coronavirus that belongs to the same family as SARS-CoV-2.

Results: Mouse hepatitis virus-A59, or its isogenic spike protein recombinant strains, inoculation in mice provides an important experimental model to understand underpinning mechanisms of neuroinflammatory demyelination in association with acute stage optic nerve inflammation and chronic stage optic nerve demyelination concurrent with axonal loss. Spike is a surface protein that mediates viral binding and entry into host cells, as well as cell-cell fusion and viral spread. Studies have implicated spike-mediated mechanisms of virus-induced neuroinflammatory demyelination by comparing naturally occurring demyelinating (DM) and nondemyelinating (NDM) MHV strains.

Conclusions: Here, we summarize findings in MHV-induced experimental ON and myelitis, using natural DM and NDM strains as well as engineered recombinant strains of MHV to understand the role of spike protein in inducing ON and demyelinating disease pathology. Potential parallels in human coronavirus-mediated ON and demyelination, and insight into potential therapeutic strategies, are discussed.

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冠状病毒尖峰蛋白在诱发小鼠视神经炎中的作用:与 SARS-CoV-2 病毒相似。
背景:视神经炎(ON)是人类神经系统疾病多发性硬化症(MS)的临床表现之一,在感染 COVID-19 的患者中也有报道,这突显了 SARS-CoV-2 的一种潜在的神经系统表现。然而,人们对这些患者出现 ON 的机制知之甚少:证据获取:通过研究具有神经毒性的小鼠肝炎病毒(MHV-A59)可能会有所发现,MHV-A59是一种β-冠状病毒,与SARS-CoV-2属于同一家族:结果:小鼠肝炎病毒-A59或其同源穗状病毒重组株接种小鼠,为了解急性期视神经炎症和慢性期视神经脱髓鞘同时伴有轴突丢失的神经炎性脱髓鞘的基本机制提供了一个重要的实验模型。尖峰蛋白是一种表面蛋白,可介导病毒结合和进入宿主细胞,以及细胞-细胞融合和病毒传播。研究通过比较自然发生的脱髓鞘型(DM)和非脱髓鞘型(NDM)MHV 株系,揭示了尖峰介导的病毒诱导神经炎性脱髓鞘机制:在此,我们总结了MHV诱导的实验性ON和脊髓炎的研究结果,利用天然DM和NDM株系以及MHV的工程重组株系来了解尖峰蛋白在诱导ON和脱髓鞘疾病病理学中的作用。本文讨论了人类冠状病毒介导的ON和脱髓鞘的潜在相似之处,并深入探讨了潜在的治疗策略。
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来源期刊
Journal of Neuro-Ophthalmology
Journal of Neuro-Ophthalmology 医学-临床神经学
CiteScore
2.80
自引率
13.80%
发文量
593
审稿时长
6-12 weeks
期刊介绍: The Journal of Neuro-Ophthalmology (JNO) is the official journal of the North American Neuro-Ophthalmology Society (NANOS). It is a quarterly, peer-reviewed journal that publishes original and commissioned articles related to neuro-ophthalmology.
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