Evaluation of a θ-defensin in a murine model of herpes simplex virus type 1 keratitis
Evaluation of a θ-defensin in a murine model of herpes simplex virus type 1 keratitis
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DOI：
10.1167/iovs.07-0302
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发表时间：
2007-11-01
影响因子：
4.4
通讯作者：
Lehrer, Robert I.
中科院分区：
文献类型：
--
作者：
Brandt, Curtis R.;Akkarawongsa, Radeekorn;Lehrer, Robert I.
目的.目的检测合成的防御素--逆转录细胞周期蛋白（RC）-2在鼠单纯疱疹病毒（HSV）-1角膜炎模型中的活性。通过产量减少和病毒灭活测定来确定RC- 2对HSV- 1科斯的体外抗病毒活性。在实验性鼠HSV- 1角膜炎模型中，使用含或不含2%甲基纤维素的PBS中的0.1%肽进行感染前或感染后治疗来测试功效。泪液膜中的病毒滴度通过空斑试验测定。RC- 2在体外抑制HSV- 1科斯，在产量降低试验中的EC 50为10 μ M（类似于20 μ g/mL），但不直接杀病毒. RC- 106（活性较低的类似物）在培养物中不抑制HSV- 1科斯。在病毒感染前，将病毒与RC- 2一起孵育或将2%甲基纤维素中的肽应用于角膜，可显著降低眼部疾病的严重程度，但感染后用含或不含2%甲基纤维素的PBS中的0.1%RC- 2治疗则无此作用。在感染后的几天内，预孵育组和预防组的病毒滴度显著降低。RC- 2在培养物中对HSV- 1科斯有活性，并且当以预防模式使用时在体内显示出保护活性，但是该肽在感染后疱疹性角膜炎模型中显示出有限的活性。这些发现支持了从HIV-1、HSV-2和甲型流感病毒实验中获得的数据，表明RC抑制病毒进入而不是它们的复制。
PURPOSE. To test the activity of a synthetic theta-defensin, retrocyclin ( RC)- 2, in a murine herpes simplex virus ( HSV)-1 keratitis model.METHODS. The in vitro antiviral activity of RC- 2 against HSV- 1 KOS was determined by yield reduction and viral inactivation assays. Efficacy in an experimental murine HSV- 1 keratitis model was tested using pre- or postinfection treatment with 0.1% peptide in PBS with or without 2% methylcellulose. Viral titers in the tear film were determined by plaque assay.RESULTS. RC- 2 inhibited HSV- 1 KOS in vitro with an EC50 of 10 mu M (similar to 20 mu g/mL) in yield- reduction assays, but was not directly virucidal. RC- 106 ( a less active analogue) did not inhibit HSV- 1 KOS in culture. Incubating the virus with RC- 2 or applying the peptide in 2% methylcellulose to the cornea before viral infection significantly reduced the severity of ocular disease, but postinfection treatment with 0.1% RC- 2 in PBS with or without 2% methylcellulose did not. Viral titers were significantly reduced on some days after infection in the preincubation and prophylaxis groups.CONCLUSIONS. RC- 2 was active against HSV- 1 KOS in cultures and showed protective activity in vivo when used in a prophylactic mode, but the peptide showed limited activity in a postinfection herpes keratitis model. These findings support data obtained from experiments with HIV-1, HSV-2, and influenza A, indicating that RCs inhibit the entry of viruses rather than their replication.