IN-VITRO INHIBITION OF HUMAN CYTOMEGALOVIRUS REPLICATION IN HUMAN FORESKIN FIBROBLASTS AND ENDOTHELIAL-CELLS BY ASCORBIC-ACID 2-PHOSPHATE
IN-VITRO INHIBITION OF HUMAN CYTOMEGALOVIRUS REPLICATION IN HUMAN FORESKIN FIBROBLASTS AND ENDOTHELIAL-CELLS BY ASCORBIC-ACID 2-PHOSPHATE
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DOI：
10.1016/0166-3542(95)00024-g
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发表时间：
1995-08-01
影响因子：
7.6
通讯作者：
DOERR, HW
中科院分区：
文献类型：
--
作者：
CINATL, J;CINATL, J;DOERR, HW
在体外培养的人包皮成纤维细胞和血管内皮细胞上，检测了L抗坏血酸-2-磷酸长效衍生物对几种人巨细胞病毒株的抗病毒活性。ASC-2P在0.2~2 mM浓度范围内对表达72 kDa CMV即刻早期抗原(IEA)的细胞数无影响，但对68 kDa晚期抗原(LA)的表达有抑制作用(EC和HFF分别减少30%和55%)。在HFF细胞中，当在CMV感染后加入ASC-2P时，病毒产量最多减少4倍。经ASC-2P处理后，细胞的抗病毒作用明显增强。经0.2 mM ASC-2P处理3代(18d)的HFF和EC中，表达IEA(EC和HFF分别减少75%和80%)和LA(EC和HFF分别减少92%和90%)的细胞显著减少。用ASC-2P进行三次继代培养，EC和HFF的病毒产量分别是EC和HFF的50-100倍和100-1000倍。ASC-2P的抗病毒活性不需要持续存在。在ASC-2P细胞中，更昔洛韦和磷甲酸钠对病毒复制的抑制作用明显高于未经处理的对照组。结果表明，ASC-2P为L抗坏血酸提供了持久的抗CMV活性。Asc-2P可能有助于CMV感染的辅助治疗。
Antiviral activity of L-ascorbic acid-2-phosphate (ASC-2P), a long-acting derivative of L-ascorbic acid, against several human cytomegalovirus (CMV) strains was examined in cultures of human foreskin fibroblasts (HFF) and endothelial cells (EC). ASC-2P at concentrations ranging from 0.2 to 2 mM had no effect on the number of cells expressing 72 kDa CMV immediate early antigen (IEA) while it inhibited expression of 68 kDa late antigen (LA) in infected cultures of both cell types (30% and 55% reduction for EC and HFF, respectively). In HFF cells, virus yield was reduced up to 4-fold, when ASC-2P was added after CMV infection. Antiviral effects were significantly increased in cultures pretreated with ASC-2P. In HFF and EC pretreated for three subcultures (18 days) with 0.2 mM ASC-2P, a significant reduction of cells expressing IEA (75% and 80% reduction in EC and HFF, respectively) and LA (92% and 90% reduction for EC and HFF, respectively) was observed. Pretreatment for three subcultures with ASC-2P inhibited virus yield 50- to 100- fold in EC and 100- to 1000-fold in HFF. The continuous presence of ASC-2P was not required for its antiviral activity. A significantly higher reduction of virus replication with ganciclovir and foscarnet was obtained in ASC-2P pretreated cells than in untreated controls. The results showed that ASC-2P provides L-ascorbic acid with long-lasting antiviral activity against CMV. ASC-2P may be of benefit for the adjunctive treatment of CMV infection.