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, JIAE - Chung-Ang University; LEE, SOOYEON - Chung-Ang University; SONG, KI-DUK - Jeongbuk National University; CHA, JIHYE - National Institute Of Veterinary Research; DANG, HOANG - National Institute Of Veterinary Research; TRAN, HA - 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: 5/13/2021
Publication Date: 6/7/2021
Citation: Vu, T.H., Hong, Y., Truong, A.D., Lee, J., Lee, S., Song, K., Cha, J., Dang, H.V., Tran, H.T., Lillehoj, H.S., Hong, Y.H. 2021. Cytokine-cytokine receptor interactions in the highly pathogenic avian influenza H5N1 virus-infected lungs of genetically disparate Ri chicken lines. Journal of Animal Bioscience. 35 (3):367-376. https://doi.org/10.5713/ab.21.0163.
DOI: https://doi.org/10.5713/ab.21.0163

Interpretive Summary: Limited information on the nature of host immunity against many poultry pathogens limits our ability to develop effective strategies for the prevention of many important infectious diseases. Avian influenza (AI) is a virus that causes severe respiratory infections in commercial poultry and there are no effective vaccines against highly pathogenic strains of AI (HPAI). There is a timely need to develop prevention strategies against viral strains which cause HPAI to reduce economic losses due to these highly contagious infections. This paper describes collaborative research between ARS scientists and scientists in Korea and Vietnam in the areas of host-pathogen immunopathology to better understand host immune response to viral infections. One of the key determinants of the severity of HPAI infection is the regulation of the host innate immune response which involves soluble factors such as cytokines and chemokines. Previous studies in various chicken models have shown that tissue damages and host death are caused by various cytokine and chemokine dysregulation in HPAI. Using chicken strains available in Vietnam, this study identified the genotypes of chickens which are resistant or susceptible to HPAIV based on their Mx and BF2 genes. When differentially expressed genes between these two strains with HPAI in the lung tissue were compared using high-throughput RNA sequencing, the expression of certain cytokines, chemokines, and IFN-stimulated genes in the resistant strains of chickens was higher than those in susceptible chickens. These results suggest that the resistant Ri chickens show higher antiviral activity compared to susceptible Ri chickens. Further in-depth studies on the underlying mode of action of these anti-viral resistance mechanisms in these chickens will enable the development of effective control strategies against HPAI.

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. 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-'), 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.