单纯疱疹病毒1型与小鼠背根神经节外植体中3 - O - 硫酸化硫酸乙酰肝素的相互作用以及病毒感染期间炎症标志物的概况。
HSV-1 interaction to 3-O-sulfated heparan sulfate in mouse-derived DRG explant and profiles of inflammatory markers during virus infection.
作者信息
Sharthiya Harsh, Seng Chanmoly, Van Kuppevelt T H, Tiwari Vaibhav, Fornaro Michele
机构信息
Department of Anatomy, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL, 60515, USA.
Department of Biomedical sciences, College of Health Sciences, Midwestern University, Downers Grove, IL, 60515, USA.
出版信息
J Neurovirol. 2017 Jun;23(3):483-491. doi: 10.1007/s13365-017-0521-4. Epub 2017 Mar 21.
The molecular mechanism of herpes simplex virus (HSV) entry and the associated inflammatory response in the nervous system remain poorly understood. Using mouse-derived ex vivo dorsal root ganglia (DRG) explant model and single cell neurons (SCNs), in this study, we provided a visual evidence for the expression of heparan sulfate (HS) and 3-O-sulfated heparan sulfate (3-OS HS) followed by their interactions with HSV-1 glycoprotein B (gB) and glycoprotein D (gD) during cell entry. Upon heparanase treatment of DRG-derived SCN, a significant inhibition of HSV-1 entry was observed suggesting the involvement of HS role during viral entry. Finally, a cytokine array profile generated during HSV-1 infection in DRG explant indicated an enhanced expression of chemokines (LIX, TIMP-2, and M-CSF)-known regulators of HS. Taken together, these results highlight the significance of HS during HSV-1 entry in DRG explant. Further investigation is needed to understand which isoforms of 3-O-sulfotransferase (3-OST)-generated HS contributed during HSV-1 infection and associated cell damage.
单纯疱疹病毒（HSV）进入神经系统的分子机制以及相关的炎症反应仍知之甚少。在本研究中，我们使用源自小鼠的离体背根神经节（DRG）外植体模型和单细胞神经元（SCN），为硫酸乙酰肝素（HS）和3 - O - 硫酸化硫酸乙酰肝素（3 - OS HS）的表达提供了可视化证据，随后在细胞进入过程中它们与HSV - 1糖蛋白B（gB）和糖蛋白D（gD）相互作用。在用乙酰肝素酶处理源自DRG的SCN后，观察到HSV - 1进入受到显著抑制，这表明HS在病毒进入过程中发挥了作用。最后，DRG外植体中HSV - 1感染期间产生的细胞因子阵列图谱表明趋化因子（LIX、TIMP - 2和M - CSF）——已知的HS调节剂——表达增强。综上所述，这些结果突出了HS在DRG外植体中HSV - 1进入过程中的重要性。需要进一步研究以了解3 - O - 磺基转移酶（3 - OST）产生的HS的哪些异构体在HSV - 1感染和相关细胞损伤过程中发挥作用。
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