Herpes keratitis in the absence of anterograde transport of virus from sensory ganglia to the cornea
Herpes keratitis in the absence of anterograde transport of virus from sensory ganglia to the cornea
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DOI：
10.1073/pnas.0503230102
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发表时间：
2005-08-09
影响因子：
11.1
通讯作者：
Johnson, DC
中科院分区：
文献类型：
--
作者：
Polcicova, K;Biswas, PS;Johnson, DC
单纯疱疹性角膜基质炎是一种发生于角膜基质的免疫病理性疾病，可导致角膜瘢痕、混浊和失明，是常见角膜手术中的重要问题。特别地，病毒抗原主要集中在角膜的上皮层中而不是基质层中，并且病毒抗原在基质炎症发展之前被消除。目前尚不清楚是什么驱动炎症，病毒抗原是否是必要的，或者病毒抗原如何到达基质。有人提出单纯疱疹病毒（HSV）从角膜上皮传播到感觉神经节，然后返回基质引起疾病。然而，也有证据表明HSV DNA和感染性病毒在角膜中持续存在，并且HSV可以传播给移植受体。为了确定是否存在于角膜中的HSV会引起疱疹性角膜基质炎，我们构建了一个HSV US 9（-）突变体，该突变体在神经元轴突中的移动能力减弱。US 9- HSV在小鼠角膜上皮和三叉神经节中正常复制和传播。然而，US 9（-）HSV不能从神经节返回到角膜，也不能引起眼周皮肤病，这需要从神经元带状疱疹样传播。然而，US 9（-）HSV引起角膜炎。因此，疱疹性角膜炎可能在没有从神经节到角膜的顺行转运的情况下发生，这可能是由角膜中持续存在的病毒介导的。
Herpes stromal keratitis is an immunopathologic disease in the corneal stroma leading to scarring, opacity, and blindness, and it is an important problem in common corneal surgeries. Paradoxically, virus antigens are largely focused in the epithelial layer of the cornea and not in the stromal layer, and viral antigens are eliminated before stromal inflammation develops. It is not clear what drives inflammation, whether viral antigens are necessary, or how viral antigens reach the stroma. It has been proposed that herpes simplex virus (HSV) travels from the corneal epithelium to sensory ganglia then returns to the stroma to cause disease. However, there is also evidence of HSV DNA and infectious virus persistent in corneas, and HSV can be transmitted to transplant recipients. To determine whether HSV resident in the cornea could cause herpes stromal keratitis, we constructed an HSV US9(-) mutant that had diminished capacity to move in neuronal axons. US9- HSV replicated and spread normally in the mouse corneal epithelium and to the trigeminal ganglia. However, US9(-) HSV was unable to return from ganglia to the cornea and failed to cause periocular skin disease, which requires zosteriform spread from neurons. Nevertheless, US9(-) HSV caused keratitis. Therefore, herpes keratitis can occur without anterograde transport from ganglia to the cornea, probably mediated by virus persistent in the cornea.