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Inhibition of rubella virus replication by the broad-spectrum drug nitazoxanide in cell culture and in a patient with a primary immune deficiency
Antiviral Research ( IF 7.6 ) Pub Date : 2017-09-30 , DOI: 10.1016/j.antiviral.2017.09.019
Ludmila Perelygina , Timo Hautala , Mikko Seppänen , Adebola Adebayo , Kathleen E. Sullivan , Joseph Icenogle

Persistent rubella virus (RV) infection has been associated with various pathologies such as congenital rubella syndrome, Fuchs's uveitis, and cutaneous granulomas in patients with primary immune deficiencies (PID). Currently there are no drugs to treat RV infections. Nitazoxanide (NTZ) is an FDA-approved drug for parasitic infections, and has been recently shown to have broad-spectrum antiviral activities. Here we found that empiric 2-month therapy with oral NTZ was associated in the decline/elimination of RV antigen from lesions in a PID patient with RV positive granulomas, while peginterferon treatment had no effect. In addition, we characterized the effects of NTZ on cell culture models of persistent RV infection. NTZ significantly inhibited RV replication in a primary culture of human umbilical vein endothelial cells (HUVEC) and Vero and A549 epithelial cell lines in a dose dependent manner with an average 50% inhibitory concentration of 0.35 μg/ml (1.1 μM). RV strains representing currently circulating genotypes were inhibited to a similar extent. NTZ affected early and late stages of infection by inhibiting synthesis of cellular and RV RNA and interfering with intracellular trafficking of the RV surface glycoproteins, E1 and E2. These results suggest a potential application of NTZ for the treatment of persistent rubella infections, but more studies are required.



中文翻译:

广谱药物nitazoxanide在细胞培养物中和原发性免疫缺陷患者中抑制风疹病毒复制

持续性风疹病毒(RV)感染与多种疾病有关,例如原发性风疹综合症,Fuchs葡萄膜炎和原发性免疫缺陷(PID)患者的皮肤肉芽肿。目前尚无用于治疗RV感染的药物。Nitazoxanide(NTZ)是FDA批准的用于寄生虫感染的药物,最近被证明具有广谱抗病毒活性。在这里,我们发现经验丰富的2个月口服NTZ治疗与RV阳性肉芽肿的PID患者的病变中RV抗原的减少/消除相关,而聚乙二醇干扰素治疗无效。此外,我们表征了NTZ对持续性RV感染的细胞培养模型的影响。NTZ以剂量依赖性方式显着抑制人脐静脉内皮细胞(HUVEC)和Vero和A549上皮细胞系原代培养中的RV复制,平均抑制浓度为0.35μg/ ml(1.1μM)。代表当前正在传播的基因型的RV菌株受到了相似程度的抑制。NTZ通过抑制细胞和RV RNA的合成并干扰RV表面糖蛋白E1和E2的细胞内运输来影响感染的早期和晚期。这些结果表明NTZ在治疗持续性风疹感染中的潜在应用,但需要更多的研究。代表当前正在传播的基因型的RV菌株受到了相似程度的抑制。NTZ通过抑制细胞和RV RNA的合成并干扰RV表面糖蛋白E1和E2在细胞内的运输来影响感染的早期和晚期。这些结果表明NTZ在治疗持续性风疹感染方面有潜在的应用前景,但还需要更多的研究。代表当前正在传播的基因型的RV菌株受到了相似程度的抑制。NTZ通过抑制细胞和RV RNA的合成并干扰RV表面糖蛋白E1和E2在细胞内的运输来影响感染的早期和晚期。这些结果表明NTZ在治疗持续性风疹感染方面有潜在的应用前景,但还需要更多的研究。

更新日期:2017-09-30
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