Objective: The highly pathogenic avian influenza virus (HPAIV) is a threat to the poultry industry as well as the economy and remains a potential source of pandemic infection in humans. Antiviral genes are considered a potential factor for HPAIV resistance. Therefore, in this study, we investigated gene expression related to cytokine-cytokine receptor interactions by comparing resistant and susceptible Ri chicken lines for avian influenza virus infection.

Methods: Ri chickens of resistant (Mx/A; BF2/B21) and susceptible (Mx/G; BF2/B13) lines were selected by genotyping the Mx and BF2 genes. These chickens were then infected with HPAIV H5N1, and their lung tissues were collected for RNA sequencing.

Results: In total, 972 differentially expressed genes (DEGs) were observed between resistant and susceptible Ri chickens, according to the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. In particular, DEGs associated with cytokine-cytokine receptor interactions were most abundant. The expression levels of cytokines (IL-1β, IL-6, IL-8, and IL-18), chemokines (CCL4 and CCL17), interferons (IFN-γ), and IFN-stimulated genes (Mx1, CCL19, OASL, and PRK) were higher in H5N1-resistant chickens than in H5N1-susceptible chickens.

Conclusion: Resistant chickens show stronger immune responses and antiviral activity (cytokines, chemokines, and IFN-stimulated genes) than those of susceptible chickens against HPAIV infection.