Cytokine-cytokine receptor interactions in the highly pathogenic avian influenza H5N1 virus-infected lungs of genetically disparate Ri chicken lines

Authors: VU, THI - Chung-Ang University; HONG, YEOJIN - Chung-Ang University; TRUONG, ANH - National Institute Of Veterinary Research; LEE, JIAC - Chung-Ang University; LEE, SOOYEON - Chung-Ang University; SONG, KI-DUC - Jeonbuk National University; CHA, JIHYE - National Institute Of Animal Science; DANG, VU - National Institute Of Veterinary Research; TRAN, HA TT - National Institute Of Veterinary Research; Lillehoj, Hyun; HONG, YEONG - Chung-Ang University

Submitted to: Journal of Animal Bioscience
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/18/2021
Publication Date: 1/5/2022
Citation: Vu, T.H., Hong, Y., Truong, A.D., Lee, J., Lee, S., Song, K., Cha, J., Dang, V.D., Tran, H., Lillehoj, H.S., Hong, Y.H. 2022. Cytokine-cytokine receptor interactions in the highly pathogenic avian influenza H5N1 virus-infected lungs of genetically disparate Ri chicken lines. Journal of Animal Bioscience. https://doi.org/10.5713/ab.21.0420.
DOI: https://doi.org/10.5713/ab.21.0420

Interpretive Summary: Limited knowledge on the host-pathogen immunobiology in avian influenza (AI) infection hinders the development of efficacious vaccines against AI in chickens. AI is caused by Influenzavirus A virus and the highly pathogenic avian influenza (HPAI) is associated with high mortality in birds. Moreover, the H5N1 virus is a threat to the poultry industry and remains a potential source of pandemic infection in humans. In this paper which describes new information on host-pathogen interaction in AI in resistant and susceptible chickens, ARS scientists in Beltsville collaborated with scientists in Vietnam and South Korea to demonstrate the importance of host immunity and the role of cytokines in protection against HPAI. Previous studies have shown a significant association of chicken’s genetic type such as the BF2 genotype with resistance or susceptibility to many pathogens including AI virus. In AI infection, cytokines and chemokines play crucial roles in pathogenesis and host death. Furthermore, regulation of cytokine-cytokine receptor interactions has been shown to be important in host defense against AI infection. In this study which was carried out in Vietnam, the expression of genes related to cytokine-cytokine receptor interactions between resistant and susceptible Ri chickens (a local chicken breed in Vietnam) was investigated using high-throughput RNA sequencing. The results showed that the expression of certain cytokines and chemokines in resistant chickens was higher than those in susceptible chickens in HPAI-infected Ri chickens. These results will enhance our knowledge on AI immunopathology and facilitate the development of novel therapeutics to control AI infection.

Technical Abstract: 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-1ß, IL-6, IL-8, and IL-18), chemokines (CCL4 and CCL17), interferons (IFN-gamma), 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 susceptible chickens against HPAIV infection.