Andersson Ida, Lundkvist Ake, Haller Otto, Mirazimi Ali
Center for Microbiological Preparedness/Swedish Institute for Infectious Disease Control, Karolinska Intitutet, Stockholm, Sweden.
J Med Virol. 2006 Feb;78(2):216-22. doi: 10.1002/jmv.20530.
Crimean-Congo hemorrhagic fever virus (CCHFV) is a causative agent of severe hemorrhagic fever occurring sporadically in parts of Africa, Asia, Southeast Europe, and the Middle East. Its recent recognition as a potential agent of bioterrorism/biowarfare highlights the need for effective antiviral therapy. In this study, it is shown that human endothelial cells are permissive to CCHFV. It is also shown that interferon-alpha inhibits the growth of CCHFV in human endothelial and hepatoma cells, reducing virus yields by a factor of 100-1,000. By using a siRNA approach, it was demonstrated that the interferon-induced MxA GTPase is a major factor mediating the antiviral effect against CCHFV, in agreement with previous findings showing that recombinant MxA inhibits CCHFV replication by interacting with the viral nucleocapsid protein. The identification of intrinsic cellular resistance factors that block CCHFV replication may help in designing novel antiviral agents.
克里米亚-刚果出血热病毒(CCHFV)是一种严重出血热的病原体,在非洲、亚洲、东南欧和中东部分地区散在发生。其最近被认定为生物恐怖主义/生物战的潜在病原体,凸显了有效抗病毒治疗的必要性。在本研究中,已表明人内皮细胞对CCHFV敏感。还表明α干扰素可抑制CCHFV在人内皮细胞和肝癌细胞中的生长,使病毒产量降低100至1000倍。通过使用小干扰RNA(siRNA)方法,证明干扰素诱导的Mx A GTP酶是介导针对CCHFV抗病毒作用的主要因素,这与先前的研究结果一致,即重组Mx A通过与病毒核衣壳蛋白相互作用抑制CCHFV复制。鉴定出阻断CCHFV复制的内在细胞抗性因子可能有助于设计新型抗病毒药物。