干扰素联合无环鸟苷抑制单纯疱疹病毒

Combined effects of interferon and acyclovir on herpes simplex virus in vitro

目的 探讨干扰素 (interferon ,IFN )与无环鸟苷 (acyclovir,ACV)联合使用抑制单纯疱疹病毒 (herpessimplexvirus ,HSV)时的药效及病毒耐药性产生情况。 方法 将HSV Ⅰ分别接种于经IFN α作用 2 4h及未经IFN α处理的非洲绿猴肾细胞中 ,加入不同浓度的ACV ,培养 72h后固定、染色、清点空斑数并计算ACV的半数有效剂量 (ED50 )。将HSV Ⅰ在含ACV及IFN α与ACV的环境中连续培养 10代 ,分别在第 3、5、7和 10代测定ACV的ED50 。结果 ACV对野生HSV Ⅰ的ED50 为 14 2 .0× 10 -9mol·L-1,IFN α与ACV联合用药时ACV对野生HSV Ⅰ的ED50 为 4 7.4× 10 -9mol·L-1。HSV Ⅰ在含ACV的环境中连续培养 7代后即产生了耐药性 ,其ED50 为第 1代的 82倍 ,而HSV Ⅰ在含有ACV和IFN α的环境中培养 10代后未产生耐药性。结论 IFN和ACV联合应用具有协同作用 ,可以减少ACV的用量 ,提高疗效 ;联合用药可以有效延缓病毒对ACV耐药性的产生。

Objective To investigate the antiviral effects and drug resistance during combination treatment to herpes simplexvirus(HSV) with interferon(IFN) and acyclovir(ACV).Methods HSV Ⅰ was inculated on African green monkey kidney (VERO) cells and IFN treated VERO cells and ACV was added to the medium in various concentrations. After 72 hours incubation, plaques were counted and the 50% effective dose (ED 50 )was calculated. HSV Ⅰwas incubated in the presence of ACV and in the presence of both ACV and IFN for 10 passages. The ED 50 of ACV was determined after the 3rd,5th,7th and 10th passage.Results The ED 50 of ACV to wild HSV Ⅰ was 142.0×10 -9 mol·L -1 ,but treatment of cells with IFN for 24 hours prior to infection decreased the ED 50 of ACV to 47.4×10 -9 mol·L -1 . In the presence of ACV alone, emergence of drug resistance was observed after passage 7 with ED 50 82 times that of the wild strain, while under the combination treatment no drug resistance was observed.Conclusion Combination therapy with IFN and ACV leads to the synergistic inhibition of HSV Ⅰ and may prevent the drug resistance of HSV Ⅰ.