HSV-1 infection and pathogenesis in the tree shrew eye following corneal inoculation
HSV-1 infection and pathogenesis in the tree shrew eye following corneal inoculation
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树鼩眼角膜接种后HSV-1感染及发病机制
DOI：
10.1007/s13365-020-00837-0
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发表时间：
2020-06-01
影响因子：
3.2
通讯作者：
Zhou, Jumin
中科院分区：
文献类型：
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作者：
Li, Lihong;Li, Yan;Zhou, Jumin
单纯疱疹病毒I型（HSV-1）感染引起角膜炎症，称为单纯疱疹病毒性角膜炎（HSK），这是一种常见但严重的角膜疾病。目前还不完全清楚反复感染期间的病毒是来自三叉神经节还是眼部组织，包括视网膜和睫状神经节。由于树鼩与灵长类亲缘关系密切，且树鼩的眼睛解剖结构与人类相似，因此我们研究了树鼩的HSV-1角膜感染。我们发现HSK的症状与人类HSK相似，在急性感染期表现出典型的点状和树突状病毒性角膜炎。单纯疱疹病毒特异性病变后，观察到间质瘢痕、角膜增厚（原发性感染）、混浊和新生血管形成等并发症。在树鼩模型中，眼部接种后，角膜被感染，利用抗hsv -1抗体可以在上皮细胞和视网膜神经节细胞中检测到病毒蛋白。HSV-1转录本、ICP0、ICP4和LAT可在感染后3天（dpi）检测到，在感染后5天达到峰值。2周后，ICP4和ICP0转录本降低到基础水平，但潜伏期相关转录本（LATs）继续积累。有趣的是，在急性感染后，我们仍然在树鼩的眼睛中检测到大量活跃的HSV-1。此外，我们发现HSV-1在睫状神经节和角膜中持续存在。这些发现支持树鼩作为非人类灵长类动物HSK模型，这可能对HSK的机制研究有用。
Herpes simplex virus type I (HSV-1) infection causes inflammation in the cornea known as herpes simplex virus keratitis (HSK), a common but serious corneal disease. It is not entirely clear whether the virus during recurring infection comes from the trigeminal ganglia or the eye tissue, including the retina and ciliary ganglion. Because the tree shrew is closely related to primates and tree shrew eye anatomic structures are similar to humans, we studied HSV-1 corneal infection in the tree shrew. We found that HSK symptoms closely mimic those found in human HSK showing typical punctiform and dendritic viral keratitis during the acute infection period. Following the HSV-specific lesions, complications such as stromal scarring, corneal thickening (primary infection), opacity, and neovascularization were observed. In the tree shrew model, following ocular inoculation, the cornea becomes infected, and viral protein can be detected using anti-HSV-1 antibodies in the epithelial layer and retina neuronal ganglion cells. The HSV-1 transcripts, ICP0, ICP4, and LAT can be detected at 3 days post-infection (dpi), peaking at 5 dpi. After 2 weeks, ICP4 and ICP0 transcripts are reduced to a basal level, but the Latency Associated Transcripts (LATs) continue to accumulate. Interestingly, after the acute infection, we still detected abundant active HSV-1 in tree shrew eyes. Further, we found HSV-1 persistent in the ciliary ganglion and cornea. These findings are discussed in support of the tree shrew as a non-human primate HSK model, which could be useful for mechanistic studies of HSK.