The folate antagonist, methotrexate, is a potent inhibitor of murine and human cytomegalovirus in vitro.

The folate antagonist, methotrexate, is a potent inhibitor of murine and human cytomegalovirus in vitro.
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叶酸拮抗剂甲氨蝶呤在体外是小鼠和人类巨细胞病毒的有效抑制剂。

DOI:
10.1016/0166-3542(89)90012-0
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发表时间:
1989
期刊:
影响因子:
7.6
通讯作者:
Debs,RJ
Debs,RJ
中科院分区:
医学2区
文献类型:
--
作者:
Shanley,JD;Debs,RJ

文献摘要

被引文献

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巨细胞病毒(CMV)是免疫功能低下患者(如AIDS患者)的主要发病来源。叶酸拮抗剂尚未被探索作为抗CMV的潜在抗病毒剂。我们研究了甲氨蝶呤的影响,相比,阿昔洛韦和更昔洛韦,对小鼠巨细胞病毒(MCMV)和人巨细胞病毒(HCMV)在体外。分别在小鼠胚胎细胞或人包皮成纤维细胞中使用MCMV和HCMV的空斑试验,我们发现微摩尔浓度的甲氨蝶呤是这两种病毒的有效抑制剂。这种作用是由于叶酸的拮抗作用,因为亚叶酸消除了甲氨蝶呤的抗病毒作用,但没有消除更昔洛韦的抗病毒作用。甲氨蝶呤引起的细胞毒性似乎不足以解释抗病毒作用。甲氨蝶呤在体内抑制CMV的能力值得探索。
Cytomegalovirus (CMV) is a major source of morbidity for immunocompromised patients, such as AIDS patients. The folic acid antagonists have not been explored as potential antiviral agents against CMV. We examined the effects of methotrexate, compared to acyclovir and ganciclovir, on both murine CMV (MCMV) and human CMV (HCMV) in vitro. Using a plaque assay in mouse embryo cells or human foreskin fibroblasts for MCMV and HCMV respectively, we found that methotrexate, in micromolar concentrations, was a potent inhibitor of both viruses. This effect was due to folic acid antagonism since folinic acid abrogated the antiviral effect of methotrexate, but not ganciclovir. Cellular toxicity due to methotrexate appeared insufficient to account for the antiviral effects. The ability of methotrexate to inhibit CMV in vivo merits exploration.