Molecular mechanisms of nairovirus repliation and evasion of host innate immune responses

奈罗病毒属属于布尼亚病毒科。奈罗病毒在世界各地都有发现，主要通过蜱传播。该属的主要成员是新出现的内罗毕羊病（NSD）病毒和克里米亚-刚果出血热（CCHF）病毒。在非洲（NSD和CCHF）和欧亚大陆（CCHF）发现的NSD由于受感染牲畜的高死亡率而影响农业，并且这两个群体都可在人类中引起人畜共患疾病。鉴于我们新的全球经济，对农业和人类具有重要意义的外来病毒的出现现在是所有国家的一个严重关切，了解这些病毒的生物学是至关重要的。奈洛病毒是一种包膜颗粒，含有表面糖蛋白、RNA依赖的RNA聚合酶（RdRp）和被核衣壳蛋白封装的三片段RNA基因组。值得注意的是，纳韦病毒RdRp含有许多在其他布尼亚病毒属中没有发现的蛋白质功能域。令人惊讶的是，其中一个结构域最近被鉴定为卵巢肿瘤样（OTU）半胱氨酸蛋白酶，它通过从细胞靶蛋白中去除泛素（Ub）和干扰素刺激基因产物15 （ISG15）来拮抗先天宿主免疫防御。

The genus Nairovirus belongs to the Bunyaviridae family of viruses. Found worldwide, Nairoviruses are transmitted primarily by ticks. Prominent members of the genera are the emerging Nairobi sheep disease (NSD) virus and the Crimean-Congo hemorrhagic fever (CCHF) virus. Found in Africa (NSD and CCHF) and Eurasia (CCHF), NSD impacts agriculture due to the high mortality rate of infected livestock, and both groups can cause zoonotic disease in humans. Given our new global economy, the emergence of exotic viruses of agricultural and human importance is now a serious concern to all nations and it is essential to understand the biology of these viruses. Nairoviruses are enveloped particles that contain surface glycoprotein, RNA dependent RNA polymerase (RdRp), and a tri-segmented RNA genome that is encapsidated by nucleocapsid proteins. Remarkably, the nairovirus RdRp contains a number of protein functional domains that are not found in those of the other Bunyavirus genera. Surprisingly, one domain was recently identified as an ovarian tumor-like (OTU) cysteine protease that antagonizes innate host immune defenses by removing ubiquitin (Ub) and Interferon-Stimulated Gene Product 15 (ISG15) from cellular target proteins.