基孔肯雅病毒(CHIKV),(重新)新出现的虫媒病毒,是基孔肯雅热的病原体.迄今为止,目前尚无批准的疫苗或特异性抗病毒治疗.在发生CHIKV流行的国家,CHIKV一再对严重的经济和公共卫生影响负责。体外抗病毒试验一般在Vero-B4细胞中进行,一种来自非洲绿猴肾脏的特征良好的细胞系。在这项工作中,我们表征了来自巴西的CHIKV患者分离株(CHIKVBrazil)的细胞亲和力,传染性,繁殖和细胞损伤,并将其与高传代实验室菌株(CHIKVRoss)进行比较。感染各种细胞系(Vero-B4,A549,Huh-7,DBTRG,U251和U138)与两种病毒株,我们发现两种病毒之间有明显的差异。CHIKVBrazil在人肝癌细胞系Huh-7中不会引起细胞病变效应(CPE)。CHIKVBrazil和CHIKVRoss均未在A549人肺上皮细胞上引起CPE。发现人类星形胶质细胞衍生的胶质母细胞瘤细胞系U138和U251是两种病毒株溶解感染的有效模型,我们讨论了它们对神经源性CHIKV疾病的预测潜力。我们还检测到两种CHIKV菌株的抗病毒功效存在显着差异。一般来说,抗病毒药物利巴韦林,羟氯喹(HCQ)和T-1105在胶质母细胞瘤细胞中对CHIKVBrazil的作用似乎比Vero-B4更好。最后,我们对CHIKV分离株进行了全基因组分析,以确定其谱系,并可能解释组织范围和抗病毒化合物疗效的差异.
Chikungunya virus (CHIKV), a (re)emerging arbovirus, is the causative agent of chikungunya fever. To date, no approved vaccine or specific antiviral therapy are available. CHIKV has repeatedly been responsible for serious economic and public health impacts in countries where CHIKV epidemics occurred. Antiviral tests in vitro are generally performed in Vero-B4 cells, a well characterised cell line derived from the kidney of an African green monkey. In this work we characterised a CHIKV patient isolate from Brazil (CHIKVBrazil) with regard to cell affinity, infectivity, propagation and cell damage and compared it with a high-passage lab strain (CHIKVRoss). Infecting various cell lines (Vero-B4, A549, Huh-7, DBTRG, U251, and U138) with both virus strains, we found distinct differences between the two viruses. CHIKVBrazil does not cause cytopathic effects (CPE) in the human hepatocarcinoma cell line Huh-7. Neither CHIKVBrazil nor CHIKVRoss caused CPE on A549 human lung epithelial cells. The human astrocyte derived glioblastoma cell lines U138 and U251 were found to be effective models for lytic infection with both virus strains and we discuss their predictive potential for neurogenic CHIKV disease. We also detected significant differences in antiviral efficacies regarding the two CHIKV strains. Generally, the antivirals ribavirin, hydroxychloroquine (HCQ) and T-1105 seem to work better against CHIKVBrazil in glioblastoma cells than in Vero-B4. Finally, full genome analyses of the CHIKV isolates were done in order to determine their lineage and possibly explain differences in tissue range and antiviral compound efficacies.