Mechanism of copper-mediated inactivation of herpes simplex virus
Mechanism of copper-mediated inactivation of herpes simplex virus
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DOI：
10.1128/aac.41.4.812
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发表时间：
1997-04-01
影响因子：
4.9
通讯作者：
Lytle, CD
中科院分区：
文献类型：
--
作者：
Sagripanti, JL;Routson, LB;Lytle, CD
铜对单纯疱疹病毒（HSV）的灭活作用可通过以下还原剂在指定的相对水平下增强：抗坏血酸远大于过氧化氢>半胱氨酸。用Cu（II）和抗坏血酸盐的组合处理HSV感染的细胞完全抑制病毒空斑形成至低于感染性病毒输入的0.006%，而它对宿主哺乳动物细胞保持30%的存活率。由每升1 mg Cu（II）和每升100 mg还原剂介导的HSV存活分数的对数与反应时间呈线性关系，其中每种还原剂的动力学速率常数为-0.87min（-1）（r = 0.93）抗坏血酸，-0.10 min（-1）（r = 0.97）过氧化氢，-0.04 min（-1）（r = 0.97）半胱氨酸，金属螯合剂和过氧化氢酶的保护作用，缺乏超氧化物歧化酶的作用，自由基清除剂的部分保护作用表明铜介导的HSV灭活机制与以前报道的铜介导的DNA损伤机制相似。HSV对Cu（II）和还原剂，特别是抗坏血酸盐的敏感性，可能有助于开发治疗性抗病毒药物。
The inactivation of herpes simplex virus (HSV) by copper was enhanced by the following reducing agents at the indicated relative level: ascorbic acid much greater than hydrogen peroxide > cysteine. Treatment of HSV-infected cells with combinations of Cu(II) and ascorbate completely inhibited virus plaque formation to below 0.006% of the infectious virus input, while it maintained 30% viability for the host mammalian cells, The logarithm of the surviving fraction of HSV mediated by 1 mg of Cu(II) per liter and 100 mg of reducing agent per liter followed a linear relationship,vith the reaction time, in which the kinetic rate constant for each reducing agent was -0.87 min(-1) (r = 0.93) for ascorbate, -0.10 min(-1) (r = 0.97) for hydrogen peroxide, and -0.04 min(-1) (r = 0.97) for cysteine, The protective effects of metal chelators and catalase, the lack of effect of superoxide dismutase, and the partial protection conferred by free-radical scavengers suggest that the mechanism of copper-mediated HSV inactivation is similar to that previously reported for copper-mediated DNA damage, The sensitivity exhibited by HSV to Cu(II) and reducing agents, particularly ascorbate, might be useful in the development of therapeutic antiviral agents.