Influenza a pathway analysis of highly pathogenic avian influenza virus (H5N1) infection in genetically disparate Ri chicken lines

Authors: HONG, YEOJIN - Chung-Ang University; LEE, JIAE - Chung-Ang University; VU, THI - Chung-Ang University; LEE, SOOYEON - Chung-Ang University; HEO, JUBI - Chung-Ang University; TRUONG, ANH - National Institute Of Veterinary Research; Lillehoj, Hyun; HONG, YEONG - Chung-Ang University

Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/10/2021
Publication Date: 2/22/2022
Citation: Hong, Y., Lee, J., Vu, T.H., Lee, S., Heo, J., Truong, A.D., Lillehoj, H.S., Hong, Y.H. 2022. Influenza a pathway analysis of highly pathogenic avian influenza virus (H5N1) infection in genetically disparate Ri chicken lines. Veterinary Immunology and Immunopathology. 246:110404. https://doi.org/10.1016/j.vetimm.2022.110404.
DOI: https://doi.org/10.1016/j.vetimm.2022.110404

Interpretive Summary: Influenza A/H5N1 is a highly pathogenic (HPAIV) and contagious virus that can be transmitted to humans. There are no effective vaccines against HPAIV and there is a timely need to understand various host factors including immune response genes to develop novel strategies against HPAIV. In this study ARS scientists collaborated with scientists from universities in Korea and Vietnam to investigate the host genes which regulate host response to HPAIV using a genetically HPAIV-resistant chicken line (HPAIV-R). In a study which was carried out in Vietnam, identification of differentially expressed genes in genetically resistant and susceptible chicken lines showed that significant differences in gene expression in multiple biological functions could explain susceptibility patterns. Interestingly, in the the resistant line, the expression of many immune regulatory genes including MX1, STAT1, IRF7, and TLR3 was upregulated including the interferon (IFN) and cytokine families. These results suggest that resistance to HPAIV is controlled by dominant set of host genes that regulate host immune regulation in chickens. Further studies based on this finding will lead to a better understanding of genetic factors controlling resistance to HPAIV and novel immunotherapeutics to control HPAIV infection in chickens.

Technical Abstract: Influenza A/H5N1 virus is a highly pathogenic (HPAIV) and contagious zoonotic virus that can be transmitted to humans. In the present study, infection with this virus and differential gene expression analyses were carried out with genetically resistant and susceptible Ri chicken lines that are native to Vietnam. On day 3 post infection, total tracheal RNA was sequenced. Differentially expressed genes in the influenza A pathway, including signaling pathway-related genes, were validated via quantitative reverse transcription-PCR. The resistant and susceptible lines showed significant differences in gene expression and various multiple biological functions. Compared to expression in the susceptible line, in the resistant line, the expression of MX1, STAT1, IRF7, and TLR3 was upregulated, while that of BF1 was downregulated. Genes from the interferon (IFN) and cytokine families, which regulate the immune system, were highly expressed in the HPAIV-infected resistant line. Finally, significant differences were observed in the expression of genes encoding components of the Jak-STAT and TLR signaling pathways between the two cell lines. Collectively, our findings suggest that the HPAIV-resistant Ri chicken line should be bred with sensitive lines to improve overall nationwide resistance. Understanding the regulation of immune pathways against HPAIV will help to better understand the mechanisms of immune regulation in chickens.