Transcriptomic profiling reveals that NSDV exploits autophagy as a proviral mechanism to enhance viral replication

Nairobi sheep disease virus (NSDV), a tick-borne orthonairovirus that causes lethal hemorrhagic gastroenteritis in small ruminants, has recently expanded eastward into China. However, its molecular pathogenesis remains poorly understood. In this study, time-course transcriptomic profiling of NSDV-infected BHK-21 cells revealed a progressive reprogramming of the autophagy pathway, characterized by significant up-regulation of autophagy-related genes. Enhanced autophagosome formation and accelerated autophagosome-lysosome fusion were confirmed by electron microscopy and mRFP-GFP-LC3 flux assays. Pharmacological blockade of autophagy with chloroquine markedly reduced viral RNA accumulation and concurrently enhanced type I interferon responses, indicating that NSDV actively exploits autophagy to facilitate replication and dampen innate immunity. These findings identify autophagy as a proviral mechanism essential for optimal NSDV replication and suggest that targeting this pathway could offer a novel therapeutic strategy against emerging nairoviral infections.