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RNA-Seq analysis reveals the different mechanisms triggered by bovine and equine after infection with FMDV.
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.
© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.
Publication Date: 2024-09-17 PubMed ID: 39287214PubMed Central: PMC11406511DOI: 10.1002/vms3.1569Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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Overview
- This study investigates how bovine (cattle) and equine (horses) animals respond differently at the molecular level after infection with foot-and-mouth disease virus (FMDV).
- The research uses RNA sequencing to uncover gene expression changes that explain why horses are naturally resistant to FMDV, unlike cattle.
Background and Rationale
- Foot-and-mouth disease virus (FMDV) primarily infects cloven-hoofed animals, such as cattle and sheep, causing severe health issues including weakened physical condition, weight loss, and lowered milk production.
- Young animals suffer high mortality rates when infected, leading to major economic losses in livestock industries.
- Odd-toed ungulates like horses and donkeys show natural resistance to FMDV, but the biological mechanisms behind this resistance are unknown.
- Understanding these mechanisms can help develop better disease control methods and improve livestock production.
Research Goals
- Analyze distribution and presence of integrin receptors in cattle and horses since integrins facilitate FMDV entry into host cells.
- Use high-throughput RNA sequencing (RNA-Seq) to study gene expression changes in the nasopharyngeal epithelium — a key tissue for FMDV infection — of cattle and horses after infection.
- Identify differences in cellular processes such as apoptosis (programmed cell death) and autophagy (cellular cleaning) between the two species.
Methods
- Immunohistochemistry to detect and map the integrin receptors on nasopharyngeal tissues of cattle and horses.
- RNA-Seq to quantify global gene expression changes following FMDV infection in both species.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to categorize and interpret the biological functions impacted.
- Quantitative PCR (qPCR) to validate gene expression findings suggested by RNA-Seq data.
Key Results
- Both cattle and horses have the four integrin receptors required for FMDV to enter cells, indicating that the resistance in horses is not due to lack of viral entry points.
- Gene expression patterns in cattle after infection showed upregulation of pro-apoptotic genes such as CASP3 and CYCS, and downregulation of apoptosis-inhibiting genes NAIP and BCL2A1—indicating activation of cell death pathways.
- In contrast, horses exhibited the opposite trend: downregulation of pro-apoptotic genes and upregulation of apoptosis-inhibiting genes, suggesting they suppress cell death triggered by infection.
- In cattle, autophagy-related genes (BECN1, ATG101, ATG4B, ATG4A, ATG13, BCL2A1) were significantly downregulated, implying poor viral clearance by autophagy.
- By comparison, horses had significant upregulation of critical autophagy genes (ATG1, ATG3, ATG9, ATG12, ATG16L1), indicating a robust autophagic response likely contributing to their viral resistance.
Interpretation and Implications
- Since integrin receptors are present in both species, resistance in horses does not stem from prevention of viral entry but likely from differences in intracellular responses like apoptosis and autophagy.
- In cattle, FMDV infection promotes apoptosis and depresses autophagy, which may allow viral replication and contribute to disease symptoms.
- In horses, enhanced autophagy and suppression of apoptosis likely hinder viral replication and support cellular survival, offering a mechanism for their natural resistance to FMDV.
- These findings highlight autophagy and apoptosis as key cellular processes influencing the outcome of FMDV infection and suggest potential therapeutic targets or breeding strategies for disease resistance.
- Further research may explore manipulating these pathways to improve resistance in susceptible species and reduce the economic impact of FMDV.
Cite This Article
APA
Wu Y, Li L, Bai W, Li T, Qian X, Liu Y, Wang S, Liu C, Wan F, Zhang D, Liu Y, Wu K, Ling Y, Zhou H, Meng F, Zhang Y, Cao J.
(2024).
RNA-Seq analysis reveals the different mechanisms triggered by bovine and equine after infection with FMDV.
Vet Med Sci, 10(5), e1569.
https://doi.org/10.1002/vms3.1569 Publication
Researcher Affiliations
- College of Life Sciences, Inner Mongolia Agricultural University, Hohhot, China.
- Inner Mongolia Key Laboratory of Biomanufacturing, Hohhot, China.
- College of Life Sciences, Inner Mongolia Agricultural University, Hohhot, China.
- Inner Mongolia Key Laboratory of Biomanufacturing, Hohhot, China.
- Inner Mongolia Endemic Livestock Biotechnology Innovation Team, Hohhot, China.
- BaoTou Medical College, Baotou, China.
- College of Life Sciences, Inner Mongolia Agricultural University, Hohhot, China.
- Inner Mongolia Key Laboratory of Biomanufacturing, Hohhot, China.
- Inner Mongolia Endemic Livestock Biotechnology Innovation Team, Hohhot, China.
- Institute of Agriculture and Animal Husbandry, Xing'an League, China.
- College of Life Sciences, Inner Mongolia Agricultural University, Hohhot, China.
- Inner Mongolia Key Laboratory of Biomanufacturing, Hohhot, China.
- Inner Mongolia Endemic Livestock Biotechnology Innovation Team, Hohhot, China.
- College of Life Sciences, Inner Mongolia Agricultural University, Hohhot, China.
- Inner Mongolia Key Laboratory of Biomanufacturing, Hohhot, China.
- Inner Mongolia Endemic Livestock Biotechnology Innovation Team, Hohhot, China.
- College of Life Sciences, Inner Mongolia Agricultural University, Hohhot, China.
- Inner Mongolia Key Laboratory of Biomanufacturing, Hohhot, China.
- Inner Mongolia Endemic Livestock Biotechnology Innovation Team, Hohhot, China.
- College of Life Sciences, Inner Mongolia Agricultural University, Hohhot, China.
- Inner Mongolia Key Laboratory of Biomanufacturing, Hohhot, China.
- Inner Mongolia Endemic Livestock Biotechnology Innovation Team, Hohhot, China.
- College of Life Sciences, Inner Mongolia Agricultural University, Hohhot, China.
- Inner Mongolia Key Laboratory of Biomanufacturing, Hohhot, China.
- Inner Mongolia Endemic Livestock Biotechnology Innovation Team, Hohhot, China.
- College of Life Sciences, Inner Mongolia Agricultural University, Hohhot, China.
- Inner Mongolia Key Laboratory of Biomanufacturing, Hohhot, China.
- Inner Mongolia Endemic Livestock Biotechnology Innovation Team, Hohhot, China.
- College of Life Sciences, Inner Mongolia Agricultural University, Hohhot, China.
- Inner Mongolia Key Laboratory of Biomanufacturing, Hohhot, China.
- Inner Mongolia Endemic Livestock Biotechnology Innovation Team, Hohhot, China.
- College of Life Sciences, Inner Mongolia Agricultural University, Hohhot, China.
- Inner Mongolia Key Laboratory of Biomanufacturing, Hohhot, China.
- Inner Mongolia Endemic Livestock Biotechnology Innovation Team, Hohhot, China.
- College of Life Sciences, Inner Mongolia Agricultural University, Hohhot, China.
- Inner Mongolia Key Laboratory of Biomanufacturing, Hohhot, China.
- Inner Mongolia Endemic Livestock Biotechnology Innovation Team, Hohhot, China.
- College of Life Sciences, Inner Mongolia Agricultural University, Hohhot, China.
- Inner Mongolia Key Laboratory of Biomanufacturing, Hohhot, China.
- Inner Mongolia Endemic Livestock Biotechnology Innovation Team, Hohhot, China.
- School of Medicine, Hainan Vocational University of Science and Technology, Haikou, China.
- College of Life Sciences, Inner Mongolia Agricultural University, Hohhot, China.
- Inner Mongolia Key Laboratory of Biomanufacturing, Hohhot, China.
- Inner Mongolia Endemic Livestock Biotechnology Innovation Team, Hohhot, China.
MeSH Terms
- Animals
- Foot-and-Mouth Disease / virology
- Cattle
- Foot-and-Mouth Disease Virus / physiology
- Foot-and-Mouth Disease Virus / genetics
- Cattle Diseases / virology
- Cattle Diseases / genetics
- Cattle Diseases / metabolism
- Horses
- RNA-Seq / veterinary
- Horse Diseases / virology
- Horse Diseases / genetics
- Horse Diseases / metabolism
Grant Funding
- 2020MS03048 / Natural Science Foundation of Inner Mongolia, China
Conflict of Interest Statement
The authors declare no conflict of interest.
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