Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
PLoS One. 2011;6(7):e22160. doi: 10.1371/journal.pone.0022160. Epub 2011 Jul 15.
Herpes simplex virus infections are highly prevalent in humans. However, the current therapeutics suffer important drawbacks such as limited results in neonates, increasing occurrence of resistance and impeded treatment of stromal infections. Remarkably, interactions of herpesviruses with human mucosa, the locus of infection, remain poorly understood and the underlying mechanisms in stromal infection remain controversial.
METHODOLOGY/PRINCIPAL FINDINGS: A human model consisting of nasal respiratory mucosa explants was characterised. Viability and integrity were examined during 96 h of cultivation. HSV1-mucosa interactions were analysed. In particular, we investigated whether HSV1 is able to reach the stroma. Explant viability and integrity remained preserved. HSV1 induced rounding up and loosening of epithelial cells with very few apoptotic and necrotic cells observed. Following 16-24 h of infection, HSV1 penetrated the basement membrane and replicated in the underlying lamina propria.
CONCLUSIONS/SIGNIFICANCE: This human explant model can be used to study virus-mucosa interactions and viral mucosal invasion mechanisms. Using this model, our results provide a novel insight into the HSV1 stromal invasion mechanism and for the first time directly demonstrate that HSV1 can penetrate the basement membrane.
单纯疱疹病毒感染在人类中非常普遍。然而，目前的治疗方法存在重要的缺陷，例如在新生儿中的疗效有限、耐药性的发生率增加以及基质感染的治疗受阻。值得注意的是，单纯疱疹病毒与人类粘膜（感染部位）的相互作用仍知之甚少，基质感染的潜在机制仍存在争议。
方法/主要发现：本研究构建了一个由鼻呼吸粘膜外植体组成的人类模型，并对其进行了研究。在 96 小时的培养过程中，检测了外植体的活力和完整性。分析了 HSV1 与粘膜的相互作用。特别地，我们研究了 HSV1 是否能够到达基质。外植体的活力和完整性保持完好。HSV1 诱导上皮细胞变圆和松动，观察到很少有凋亡和坏死细胞。感染 16-24 小时后，HSV1 穿透基底膜并在下面的固有层中复制。
结论/意义：该人类外植体模型可用于研究病毒-粘膜相互作用和病毒粘膜入侵机制。使用该模型，我们的结果为 HSV1 基质入侵机制提供了新的见解，并首次直接证明 HSV1 可以穿透基底膜。
