Bluetongue virus (BTV) infects various ruminant species, posing significant threats to animal health and causing substantial economic losses to the livestock industry. Ovine type II alveolar epithelial cells (OAECIIs) play crucial roles in maintaining pulmonary structural integrity and modulating immune responses. Their dysfunction is closely associated with lung disease pathogenesis, making them important therapeutic targets. However, OAECIIs’ immunoregulatory functions and early response mechanisms during BTV infection remain unclear. To address this, we analyzed transcriptomic changes in OAECIIs following BTV-1 infection. RNA-seq revealed 1047 and 852 differentially expressed genes (DEGs) at 8 and 12 h post-infection (hpi), respectively, compared to uninfected controls. Bioinformatics analysis showed significant upregulation of nucleic acid-sensing receptors, interferon-stimulating factors, inflammatory mediators, and cytokines during early infection, mediated primarily through type I interferon signaling, TNF signaling, and cytosolic DNA-sensing pathways. We identified MAD5, ZNFX1, cGAS, OAS, PKR and ZBP1 as key pattern recognition receptors in OAECIIs during BTV infection. The IFN-β, MX1/2, RSAD2 and PLSCR1 pathways mediated antiviral responses, while IL-15, CXCL10, CCL2 triggered inflammatory responses, collectively causing structural alterations through AQP1/9 and tight junction protein modulation. These findings provide critical insights into early antiviral mechanisms and cellular structural changes in OAECIIs during BTV infection, establishing a foundation for understanding pneumonia pathogenesis and developing targeted BTV therapies.

Bluetongue virus belongs to the Reoviridae family, which causes morbidity in ruminants. Herein, we report the full-length genome sequence of a recombinant BTV strain of serotype 1 (YNDH/103/2013) isolated from sentinel cattle in Yunnan Province, China, in 2013. To identify and understand the characteristics of YNDH/103/2013, we screened closely related viruses using Simplot 3.5.1 software and conducted verification via phylogenetic analysis using MEGA 11.0.13 software. Phylogenetic analysis and segment examination showed that the YNDH/103/2013 strain likely originated from multiple recombination events involving prevalent strains such as Y863, NRT37/ABT/HSR, and YTS-4 in China and India. The genome of BTV-1/YNDH/103/2013 derives from at least three reassortments with these strains, showing recombination breakpoints mainly in segments 4, 6, 8, and 9. This study improves our understanding of the origin and spread of BTV-1 in China.