# RNA‐Seq analysis reveals the different mechanisms triggered by bovine and equine after infection with FMDV

## TL;DR

This study compares how cattle and horses respond to FMDV infection, revealing differences in gene activity that may explain why horses are naturally resistant.

## Contribution

The study identifies novel differences in apoptosis and autophagy gene expression between FMDV-susceptible cattle and resistant horses.

## Key findings

- Cattle show increased pro-apoptotic gene activity after FMDV infection, while horses show decreased activity.
- Horses upregulate autophagy-related genes after infection, suggesting a potential mechanism for viral clearance.
- Both cattle and horses have integrin receptors that allow FMDV entry, but their intracellular responses differ significantly.

## Abstract

Foot‐and‐mouth disease virus (FMDV) is an important pathogen of the MicroRNA virus family. Infection of livestock can cause physical weakness, weight loss, reduced milk production, and a significant reduction in productivity for an extended period. It also causes a high mortality rate in young animals, seriously affecting livestock production. The host range of FMDV is mainly limited to cloven‐hoofed animals such as cattle and sheep, while odd‐toed ungulates such as horses and donkeys have natural resistance to FMDV. The mechanism underlying this resistance in odd‐toed ungulates remains unclear.

This study aimed to analyze the differences between FMDV‐infected cattle and horses to provide valuable insights into the host‐FMDV interaction mechanisms, thereby contributing to the control of foot‐and‐mouth disease and promoting the development of the livestock industry.

We observed the distribution of integrins, which help FMDV enter host cells, in the nasopharyngeal tissues of cattle and horses using immunohistochemistry. Then, we employed high‐throughput RNA sequencing (RNA‐Seq) to study the changes in host gene expression in the nasopharyngeal epithelial tissues of cattle and horses after FMDV infection. We performed enrichment analysis of GO and KEGG pathways after FMDV infection and validated related genes through qPCR.

The immunohistochemical results showed that both cattle and horses had four integrin receptors that could assist FMDV entry into host cells. The transcriptome analysis revealed that after FMDV infection, pro‐apoptotic genes such as caspase‐3 (CASP3) and cytochrome C (CYCS) were upregulated in cattle, while apoptosis‐inhibiting genes such as NAIP and BCL2A1 were downregulated. In contrast, the expression trend of related genes in horses was opposite to that in cattle. Additionally, autophagy‐related genes such as beclin 1, ATG101, ATG4B, ATG4A, ATG13, and BCL2A1 were downregulated in cattle after FMDV infection, indicating that cattle did not clear the virus through autophagy. However, key autophagy genes including ATG1, ATG3, ATG9, ATG12, and ATG16L1 were significantly upregulated in horses after viral infection.

Both water buffaloes and Mongolian horses express integrin receptors that allow FMDV entry into cells. Therefore, the resistance of Mongolian horses to FMDV may result from more changes in intracellular mechanisms, including processes such as autophagy and apoptosis. Significant differences were observed between water buffaloes and Mongolian horses in these processes, suggesting that these processes influence FMDV replication and synthesis.

Both nonsusceptible animals (horses) and susceptible animals (cows) have integrin receptors in their nasopharyngeal tissues that can help FMDV enter cells.Infection with the FMDV promotes apoptosis in cows, while the opposite is true for horses.Autophagy‐related genes show a significant increase in expression in horses infected with FMDV.

Both nonsusceptible animals (horses) and susceptible animals (cows) have integrin receptors in their nasopharyngeal tissues that can help FMDV enter cells.

Infection with the FMDV promotes apoptosis in cows, while the opposite is true for horses.

Autophagy‐related genes show a significant increase in expression in horses infected with FMDV.