# Transcriptomic Analysis of the Antiviral Responses in Ovine Type II Alveolar Epithelial Cells During Early Stage of Bluetongue Virus Infection

## TL;DR

This study explores how ovine lung cells respond to bluetongue virus infection, revealing key immune pathways and structural changes that could help develop new treatments.

## Contribution

The study identifies specific genes and pathways involved in early antiviral and inflammatory responses in ovine alveolar epithelial cells during bluetongue virus infection.

## Key findings

- Early BTV infection activates interferon and inflammatory pathways in ovine alveolar epithelial cells.
- BTV infection disrupts cellular structural integrity through modulation of tight junction proteins and AQPs.
- Key pattern recognition receptors and antiviral pathways were identified in OAECIIs during early BTV infection.

## Abstract

This study systematically characterized the innate immune and inflammatory pathways activated during early BTV infection through transcriptome sequencing of BTV-infected ovine type II alveolar epithelial cells at 8 and 12 h post-infection (hpi), integrated with bioinformatics analysis and qPCR validation. Furthermore, we demonstrate that early BTV infection disrupts cellular structural integrity. These findings not only enhance our understanding of the host’s early immune response to BTV-1, but also provide critical insights into virus–host interactions and the molecular mechanisms underlying bluetongue disease pathogenesis, thereby establishing a solid experimental basis for the development of antiviral intervention strategies.

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.