Diversity of interferon inducible Mx gene in horses and association of variations with susceptibility vis-à-vis resistance against equine influenza infection.

The research article investigates the diversity of the Mx gene in horses, its role in defending against the Orthomyxo virus family, which includes the equine influenza virus, and the potential correlation between variations in this gene and susceptibility or resistance to equine influenza in Marwari horses.

Introduction and Background

• The study revolves around equine influenza (EI), a major respiratory disease of significant economic concern in horses. There is increasing concern regarding EI due to its recurrent outbreaks, cross-species transfer (as in the case of H3N8 virus in dogs), and its potential threat to form a human pandemic due to its unpredictable nature.
• One approach to combating EI is by studying the myxovirus resistance protein (Mx), which has shown in prior studies to offer resistance against Orthomyxo virus infections. The researchers’ goal is to understand the variations and antiviral activities of this Mx gene in horses, particularly the Marwari breed.

Methodology

• Blood samples were collected from horses that tested positive for equine influenza and from horses with a history of non-symptomatic contact. It’s important to include both groups to investigate potential genetic factors related to disease resistance.
• The researchers isolated specific cells – peripheral blood mononuclear cells (PBMCs) – from the blood samples and stimulated them with interferon (IFN) α/β to provoke the Mx gene.
• Using gene specific primers, the Mx gene was amplified from the total RNA isolated, and the resulting amplified products from selected samples were cloned and sequenced.
• The resulting nucleotide sequences and deduced amino acid sequences from the gene cloning were carefully analyzed.

Findings

• The researchers noted a total of 24 amino acid substitutions in the sequenced genes, with 13 predicted to have functional consequences based on their SIFT (sorting intolerant from tolerant) analysis.
• Interestingly, five of these substitutions (V67A, W123L, E346Y, N347Y, S689N) were only observed in animals that were resistant to equine influenza, suggesting a potential link between these gene variations and disease resistance.
• When assessing evolutionary distances based on the nucleotide sequences within horses, they found a range between 0.3-2.0%. Comparatively, the range was significantly higher (20-24%) when compared with other species.
• Phylogenetic analysis, which maps out the evolutionary relationship between species, showed that all equine sequences clustered together while other species formed separate groups.

Conclusion

• The data collected in the study might offer a genetic explanation for varying susceptibility to equine influenza in different horses. Specifically, certain variations in the Mx gene could be associated with resistance to the disease.
• Such findings might inform future strategies for preventing EI, such as breeding programs that favor these genetic traits or gene therapies that could offer increased disease resistance.