风疹病毒(RuV)和慢性肉芽肿之间有很强的联系,在有先天免疫错误的人中,最近成立了。RA27/3疫苗和野生型RuV毒株均对广谱抗病毒药物高度敏感,硝唑尼特(NTZ),在体外。然而,NTZ治疗,用作抢救疗法,导致患者RuV相关皮肤肉芽肿的改善很少或没有改善。这里,我们报告了对两名共济失调-毛细血管扩张症患者治疗失败的可能原因的调查.尽管通过实时RT-PCR检测到皮肤病变中RuVRNA的减少,活的免疫缺陷相关疫苗衍生的风疹病毒(iVDRV)从肉芽肿中恢复,治疗前后。替唑尼特,一种活跃的NTZ代谢物,抑制所有iVDRV在培养的A549细胞中的复制,但是50%和90%的抑制浓度比RA27/3菌株高10-40倍。iVDRV敏感性没有实质性差异,无论是在治疗之前还是治疗之后。E1基因中的准种分析,一个可疑的NTZ目标,显示NTZ处理对病变的准种复杂性没有影响。因此,NTZ疗法的失败可能是由于iVDRV对药物的敏感性低,与抵抗的出现无关,长期NTZ治疗后。
A strong association between rubella virus (RuV) and chronic granulomas, in individuals with inborn errors of immunity, has been recently established. Both the RA27/3 vaccine and wild-type RuV strains were highly sensitive to a broad-spectrum antiviral drug, nitazoxanide (NTZ), in vitro. However, NTZ treatment, used as a salvage therapy, resulted in little or no improvements of RuV-associated cutaneous granulomas in patients. Here, we report investigations of possible causes of treatment failures in two ataxia-telangiectasia patients. Although a reduction in RuV RNA in skin lesions was detected by real-time RT-PCR, live immunodeficiency-related vaccine-derived rubella viruses (iVDRV) were recovered from granulomas, before and after the treatments. Tizoxanide, an active NTZ metabolite, inhibited replications of all iVDRVs in cultured A549 cells, but the 50% and 90% inhibitory concentrations were 10-40 times higher than those for the RA27/3 strain. There were no substantial differences in iVDRV sensitivities, neither before nor after treatments. Analysis of quasispecies in the E1 gene, a suspected NTZ target, showed no effect of NTZ treatments on quasispecies\' complexity in lesions. Thus, failures of NTZ therapies were likely due to low sensitivities of iVDRVs to the drug, and not related to the emergence of resistance, following long-term NTZ treatments.