Laboratory of Clinical Virology, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece.
Laboratory of Clinical Virology, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece.
Virus Res. 2019 Jan 2;259:10-17. doi: 10.1016/j.virusres.2018.10.010. Epub 2018 Oct 16.
Intervertebral disc (IVD) degeneration has a complex multifactorial origin and it is tightly associated with changes in the secretion of proteoglycans and collagen of the Nucleus Pulposus (NP) extracellular matrix. Chronic infection by Herpes virus has been previously associated with disc degeneration after detection of Herpes Simplex Virus type-1 (HSV-1) and CMV DNA in human excised disc samples. The aim of the present study was to assess the effect of HSV-1 infection on proteoglycan synthesis employing human Nucleus Pulposus (HNPCs) cells as a model of intervertebral disc degeneration. During lytic HSV-1 infection, a significant reduction of Decorin expression was observed 8 h post infection (h.p.i) which furthered deteriorated at 24 h.p.i. Biglycan was also reduced but only 24 h.p.i. Collagen type II, although demonstrated a downward trend, it was not statistically significant, whereas both Versican and Aggrecan showed a substantial decrease at 24 h.p.i. Hyaluronan production was not significantly affected. In a non-productive HSV-1 infection, a substantial reduction of Decorin, Biglycan, Versican and Aggrecan expression was found, similarly to our findings from the lytic infection. Furthermore, collagen type II expression was completely abolished. HAS1 expression was not affected, whereas HAS 2 and 3 were found to be significantly reduced. These results indicate that HSV-1 infection of human NP cells yields a complex effect on host extracellular cell function. The viral-induced changes in proteoglycan and collagen type II concentration may affect cell-matrix interactions and lead to a dysfunctional intervertebral disc which may trigger or promote the degeneration process.
椎间盘（IVD）退变具有复杂的多因素起源，与髓核（NP）细胞外基质中蛋白聚糖和胶原蛋白分泌的变化密切相关。先前已经发现疱疹病毒的慢性感染与椎间盘退变有关，在人切除的椎间盘样本中检测到单纯疱疹病毒 1 型（HSV-1）和 CMV DNA。本研究旨在评估 HSV-1 感染对蛋白聚糖合成的影响，用人 NP 细胞（HNPCs）作为椎间盘退变的模型。在 HSV-1 裂解感染期间，观察到 8 h.p.i 时 Decorin 表达显著减少，24 h.p.i 时进一步恶化。Biglycan 也减少了，但仅在 24 h.p.i 时。尽管 II 型胶原表现出下降趋势，但无统计学意义，而 Versican 和 Aggrecan 在 24 h.p.i 时均显著减少。透明质酸的产生没有受到显著影响。在非增殖性 HSV-1 感染中，发现 Decorin、Biglycan、Versican 和 Aggrecan 的表达大量减少，与我们在裂解感染中的发现相似。此外，II 型胶原的表达完全被阻断。HAS1 表达不受影响，而 HAS2 和 HAS3 则明显减少。这些结果表明，HSV-1 感染人 NP 细胞对宿主细胞外基质功能产生复杂影响。病毒诱导的蛋白聚糖和 II 型胶原浓度的变化可能影响细胞-基质相互作用，并导致功能失调的椎间盘，这可能引发或促进退变过程。
