Immune Responses of Chickens Infected with Wild Bird-Origin H5N6 Avian Influenza Virus

Abstract

Since April 2014, new infections of H5N6 avian influenza virus (AIV) in humans and domestic poultry have caused considerable economic losses in the poultry industry and posed an enormous threat to human health worldwide. In previous research using gene sequence and phylogenetic analysis, we reported that H5N6 AIV isolated in February 2015 (ZH283) in Pallas’s sandgrouse was highly similar to that isolated in a human in December 2015 (A/Guangdong/ZQ874/2015), whereas a virus (i.e., SW8) isolated in oriental magpie-robin in 2014 was highly similar to that of A/chicken/Dongguan/2690/2013 (H5N6). However, the pathogenicity, transmissibility, and host immune-related response of chickens infected by those wild bird-origin H5N6 AIVs remain unknown. In response, we examined the viral distribution and mRNA expression profiles of immune-related genes in chickens infected with both viruses. Results showed that the H5N6 AIVs were highly pathogenic to chickens and caused not only systemic infection in multiple tissues, but also 100% mortality within 3–5 days post-infection. Additionally, ZH283 efficiently replicated in all tested tissues and transmitted among chickens more rapidly than SW8. Moreover, quantitative real-time polymerase chain reaction analysis showed that following infection with H5N6, AIVs immune-related genes remained active in a tissue-dependent manner, as well as that ZH283 induced mRNA expression profiles such as TLR3, TLR7, IL-6, TNF-α, IL-1β, IL-10, IL-8, and MHC-II to a greater extent than SW8 in the tested tissues of infected chickens. Altogether, our findings help to illuminate the pathogenesis and immunologic mechanisms of H5N6 AIVs in chickens.

Host Innate Immune Response of Geese Infected with Clade 2.3.4.4 H5N6 Highly Pathogenic Avian Influenza Viruses

“…Notably, treatment with recombinant chicken IFN-α also failed to confer protection against H5N1 HPAIV challenge in chicken [58]. Similarly, a significant upregulation of IFNs (α/β/γ) was induced in the lungs of H5N6 infected chickens, but none of these infected chickens survived [59]. In this study, the expression of IFN-α, IFN-γ, Mx, and OASL was also upregulated in the lungs and spleens of H5N6 inoculated geese, but the viral titers continued to increase in these organs and most of the inoculated geese died within 14 days.…”

Immune-Related Gene Expression in Ducks Infected With Waterfowl-Origin H5N6 Highly Pathogenic Avian Influenza Viruses

“…Our previous studies have shown that the expression of TLR3 and RIG-I were increased in the brains of ducks infected with H5N1 HPAIV (Wei et al, 2013). In addition, the expression of TLR3 was also significantly upregulated in the lungs and brains of H5N6 HPAIVs inoculated chickens (Gao et al, 2017). In our study, TLR7, TLR3, and MDA5 were also significantly increased in the lung of ducks infected with GS16568 and DK16873 viruses at 3 DPI.…”

The Epidemiology, Virology, and Pathogenicity of Human Infections with Avian Influenza Viruses

“…Therefore, the "cytokine storm" caused by disorder of the natural immune response may be an important contributor to severe infections. Infections of chickens with the recently emerged HPAI H5N6 viruses (which have caused several human fatalities), results in a very distinct immune response relative to other H5N6 strains by inducing much higher levels of IL-6, IL-8, and other pro-inflammatory mediators such as TNF-α (Gao et al 2017).…”