RNA‐Seq analysis reveals the different mechanisms triggered by bovine and equine after infection with FMDV
Authors: Yi Wu, Lu Li, Wanfu Bai, Tao Li, Xiaoying Qian, Yiyi Liu, Shenyuan Wang, Chunxia Liu, Fang Wan, Dong Zhang, Yingchun Liu, Kaifeng Wu, Yu Ling, Huanmin Zhou, Fanhua Meng, Yanru Zhang, Junwei Cao
Journal: Veterinary Medicine and Science
Summary
# Editorial Summary Although horses possess the integrin receptors necessary for foot-and-mouth disease virus (FMDV) entry into cells, they remain naturally resistant to infection—a protection mechanism that has puzzled researchers given that susceptible cattle express the same cellular entry points. This 2024 RNA-Seq study examined nasopharyngeal tissue responses in cattle and horses following FMDV infection to identify the molecular mechanisms underlying equine resistance. Whilst infected cattle exhibited suppressed autophagy and elevated pro-apoptotic signalling (increased caspase-3 and cytochrome C, decreased NAIP and BCL2A1), horses mounted the opposing response: key autophagy genes (ATG1, ATG3, ATG9, ATG12, ATG16L1) were significantly upregulated, coupled with enhanced anti-apoptotic gene expression. The findings suggest that horses' innate resistance stems not from preventing viral entry, but from robust intracellular defences—particularly an aggressive autophagic response that effectively clears the virus before productive infection can establish—whereas the cattle's impaired autophagy allows FMDV replication to proceed unchecked. For equine practitioners, this research reinforces that horses' natural protection against FMDV is remarkably solid at the cellular level, though it underscores the importance of maintaining strict biosecurity protocols when managing horses alongside infected ruminants, since mechanistic resistance differs fundamentally between species.
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Practical Takeaways
- •Horses' natural resistance to FMDV appears mechanistic rather than due to lack of viral entry receptors, which may inform future vaccine or therapeutic development strategies
- •Understanding that equine antiviral defence relies on autophagy activation could guide development of species-specific interventions for viral diseases in horses
- •The fundamental difference in how cattle and horses respond to FMDV at the cellular level explains epidemiological patterns and may have implications for multi-species farm biosecurity protocols
Key Findings
- •Both cattle and horses express integrin receptors enabling FMDV cell entry, yet horses remain naturally resistant to infection
- •FMDV infection triggers opposing apoptotic gene expression patterns: upregulation of pro-apoptotic genes (CASP3, CYCS) in cattle versus upregulation of apoptosis-inhibiting genes (NAIP, BCL2A1) in horses
- •Autophagy-related genes (ATG1, ATG3, ATG9, ATG12, ATG16L1) were significantly upregulated in horses post-infection but downregulated in cattle, suggesting autophagy is the key antiviral mechanism in equines
- •Intracellular mechanisms including autophagy and apoptosis pathways, rather than receptor availability, determine species-specific resistance to FMDV