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

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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.