Exosomes from H5N1 avian influenza virus-infected chickens regulate antiviral immune responses of chicken immune cells

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

Submitted to: Veterinary Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/27/2022
Publication Date: 1/29/2022
Citation: Hong, Y., Truong, A.D., Vu, T.H., Lee, S., Heo, J., Kang, S., Lillehoj, H.S., Hong, Y.H. 2022. Exosomes from H5N1 avian influenza virus-infected chickens regulate antiviral immune responses of chicken immune cells. Veterinary Research. 130:104368. https://doi.org/10.1016/j.dci.2022.104368.
DOI: https://doi.org/10.1016/j.dci.2022.104368

Interpretive Summary: Effective control of infectious diseases is one of many challenges that the poultry industry faces these days and there is a timely need to develop effective prevention strategies against many viral infections such as avian influenza. The outbreak of highly pathogenic avian influenza virus (HPAIV) H5N1 causes considerable economic loss in the poultry industry. In this study, ARS scientists collaborated with scientists in Korea and Vietnam to investigate a novel molecular immunotherapeutic tool using exosomes which are cell membrane-derived vesicles found in most biological fluids such as plasma and urine. Exosomes play important roles in communication among immune cells. The results of in vivo chicken trials demonstrated that exosomes from HPAIV H5N1-infected White Leghorn chickens modulated many aspects of poultry immunity. Since the innate immune system defends the host against HPAIV H5N1 infection by inducing various pro-inflammatory cytokines, this finding supports using exosomes against AI infection prevention. Therefore, these findings enhance our understanding of the mechanism of protective host immunity and will facilitate the development of novel immune-based therapeutics against AI.

Technical Abstract: Exosomes (membrane-derived vesicles) enable intracellular communication by delivering lipids, proteins, DNA, and RNA from one cell to another. Highly pathogenic avian influenza virus (HPAIV) H5N1 causes considerable economic loss in the poultry industry and poses a public health concern. The host innate immune system defends against H5N1 infection by activating antiviral immune responses. This study was aimed to demonstrate immunomodulatory effects of exosomes from HPAIV H5N1-infected White Leghorn chickens on chicken macrophages, fibroblasts, T cell, and B cell lines. The expression of type I interferons (IFN-a and -ß) was highly upregulated in immune-related cell lines after treatment with exosomes derived from H5N1-infected chickens. Levels of pro-inflammatory cytokines, such as IFN-gamma, IL-1ß, and IL-8, were also elevated by the exosomes. The mitogen-activated protein kinase (MAPK) signaling pathway was stimulated in immune-related cells by such exosomes via phosphorylation of extracellular regulated kinases 1/2 and p38 signaling molecules. Furthermore, the H5N1 viral proteins, nucleoprotein (NP) and non-structural protein (NS1) were packaged in exosomes and successfully transferred to non-infected immune-related cells. Therefore, exosomes from H5N1-infected chickens induced pro-inflammatory cytokine expression and stimulated the MAPK signaling pathway by delivering key viral proteins. These findings will enhance our understanding of the mechanisms underlying the modulation of antiviral immune responses of host immune-related cells by viral-protein-carrying exosomes.