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α-干扰素2a与阿昔洛韦在角膜细胞中协同抗水痘带状疱疹病毒的活性

Synergistic anti-varicella-zoster virus activity of interferon-alpha 2a and acyclovir in corneal cells.

作者信息

Punda-Polić V, O'Brien W J, Taylor J L

机构信息

Department of Microbiology, University Hospital Split, Croatia.

出版信息

Zentralbl Bakteriol. 1999 Apr;289(2):203-10. doi: 10.1016/s0934-8840(99)80107-8.

DOI:10.1016/s0934-8840(99)80107-8
PMID:10360320
Abstract

Human corneal stromal (HCS) cells in cultures established from donor corneas can serve as host cells for replication of varicella-zoster virus (VZV). Comparative infectious centers assays suggest that HCS cells are more restrictive hosts than MRC-5 cells, a line of human embryonic lung fibroblasts, commonly used for VZV isolation. VZV propagated in MRC-5 cells was infectious for both MRC-5 and HCS cells, but titers in HCS were one fifth of those in MRC-5 cells. Inhibition of VZV replication in HCS cells by acyclovir (ACV), recombinant human interferon-alpha 2a (IFN-alpha 2a), or the combination of these two antivirals was detected by both an infectious centers-plaque-reduction assay and an ELISA method using monoclonal anti-VZV antibody. In the infectious centers-plaque-reduction assay combinations of ACV with IFN-alpha 2a showed synergistic anti-VZV activity. VZV protein synthesis, as detected by the ELISA, was a less sensitive measure of the antiviral effects producing an ED50 value of 50 microM for ACV, five to ten times the ED50 determined in the plaque reduction assay. In the ELISA, high titers of IFN-alpha 2a (2000 IU/ml) decreased virus antigen expression only slightly, while combinations of ACV and IFN-alpha 2a were synergistic in their detected anti-VZV activity. These data document the replication of VZV in HCS cells and demonstrate that VZV is sensitive to the synergistic antiviral action of combinations of IFN-alpha 2a and ACV.

摘要

从供体角膜建立的培养物中的人角膜基质(HCS)细胞可作为水痘带状疱疹病毒(VZV)复制的宿主细胞。比较感染中心试验表明,HCS细胞比MRC - 5细胞(一种常用于VZV分离的人胚肺成纤维细胞系)更具限制性。在MRC - 5细胞中增殖的VZV对MRC - 5和HCS细胞均具有感染性,但在HCS细胞中的滴度是MRC - 5细胞中的五分之一。通过感染中心蚀斑减少试验和使用单克隆抗VZV抗体的ELISA方法检测到阿昔洛韦(ACV)、重组人干扰素α - 2a(IFN - α - 2a)或这两种抗病毒药物的组合对HCS细胞中VZV复制的抑制作用。在感染中心蚀斑减少试验中,ACV与IFN - α - 2a的组合显示出协同抗VZV活性。ELISA检测到的VZV蛋白合成对抗病毒作用的敏感性较低,ACV的ED50值为50 microM,是蚀斑减少试验中确定的ED50的五到十倍。在ELISA中,高滴度的IFN - α - 2a(2000 IU/ml)仅轻微降低病毒抗原表达,而ACV和IFN - α - 2a的组合在其检测到的抗VZV活性中具有协同作用。这些数据记录了VZV在HCS细胞中的复制,并证明VZV对IFN - α - 2a和ACV组合的协同抗病毒作用敏感。

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Synergistic anti-varicella-zoster virus activity of interferon-alpha 2a and acyclovir in corneal cells.α-干扰素2a与阿昔洛韦在角膜细胞中协同抗水痘带状疱疹病毒的活性
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引用本文的文献

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Varicella-zoster virus open reading frame 66 protein kinase is required for efficient viral growth in primary human corneal stromal fibroblast cells.水痘-带状疱疹病毒开放阅读框66蛋白激酶是原发性人角膜基质成纤维细胞中病毒高效生长所必需的。
J Virol. 2008 Aug;82(15):7653-65. doi: 10.1128/JVI.00311-08. Epub 2008 May 21.