Nairobi sheep disease virus: an emerging threat with unresolved pathogenesis and zoonotic potential

Nairobi sheep disease virus (NSDV), a tick-borne orthonairovirus, causes severe hemorrhagic disease in small ruminants with mortality rates reaching 90% in naïve populations. Its recent emergence in China, the world's largest small ruminant producer, marks a significant eastward expansion and poses immediate threats to global food security and animal health. This escalating crisis, however, stands in stark contrast to critical gaps in understanding the virus's molecular pathogenesis. The mechanisms governing cellular entry, innate immune evasion, and induction of lethal vascular pathology remain poorly characterized, severely hampering countermeasure development. This review synthesizes the current epidemiological landscape of NSDV and delineates key knowledge gaps in its molecular biology. We place particular emphasis on the unexplored viral life cycle and the host response and conclude by proposing a prioritized research agenda aimed at bridging these mechanistic gaps. Within a One Health framework, such efforts are essential to mitigate the veterinary, economic, and potential zoonotic impacts of this emerging arthropod-borne threat.