Chicken IFI6 inhibits avian reovirus replication and affects related innate immune signaling pathways

Abstract

Interferon-alpha inducible protein 6 (IFI6) is an important interferon-stimulated gene. To date, research on IFI6 has mainly focused on human malignant tumors, virus-related diseases and autoimmune diseases. Previous studies have shown that IFI6 plays an important role in antiviral, antiapoptotic and tumor-promoting cellular functions, but few studies have focused on the structure or function of avian IFI6. Avian reovirus (ARV) is an important virus that can exert immunosuppressive effects on poultry. Preliminary studies have shown that IFI6 expression is upregulated in various tissues and organs of specific-pathogen-free chickens infected with ARV, suggesting that IFI6 plays an important role in ARV infection. To analyze the function of avian IFI6, particularly in ARV infection, the chicken IFI6 gene was cloned, a bioinformatics analysis was conducted, and the roles of IFI6 in ARV replication and the innate immune response were investigated after the overexpression or knockdown of IFI6 in vitro. The results indicated that the molecular weight of the chicken IFI6 protein was approximately 11 kDa and that its structure was similar to that of the human IFI27L1 protein. A phylogenetic tree analysis of the IFI6 amino acid sequence revealed that the evolution of mammals and birds was clearly divided into two branches. The evolutionary history and homology of chickens are similar to those of other birds. Avian IFI6 localized to the cytoplasm and was abundantly expressed in the chicken lung, intestine, pancreas, liver, spleen, glandular stomach, thymus, bursa of Fabricius and trachea. Further studies demonstrated that IFI6 overexpression in DF-1 cells inhibited ARV replication and that the inhibition of IFI6 expression promoted ARV replication. After ARV infection, IFI6 modulated the expression of various innate immunity-related factors. Notably, the expression patterns of MAVS and IFI6 were similar, and the expression patterns of IRF1 and IFN-β were opposite to those of IFI6. The results of this study further advance the research on avian IFI6 and provide a theoretical basis for further research on the role of IFI6 in avian virus infection and innate immunity.

Analysis of Chicken IFITM3 Gene Expression and Its Effect on Avian Reovirus Replication

“…IFITM3 also significantly improves the incidence of colitis and prevents inflammation-associated tumorigenesis. After ARV infection, the virus replicates primarily in the host’s gut and subsequently spreads through the fecal-oral route and respiratory tract [ 1 , 36 , 37 ]. However, whether ARV infection further induces the expression of the IFITM3 gene in the gut is unknown.…”

Transcriptional Signatures of Domestication Revealed by Meta-Analysis of Pig, Chicken, Wild Boar, and Red Junglefowl Gene Expression Data

“…In contrast, seven genes (MAFF, HSPB8, BAG3, TAGLN, POPDC2, SCN1B, and NT5C1A) were commonly upregulated in wild boars (206 genes) and red junglefowl (200 genes). The upregulated genes in the domesticated animals were involved in various biological processes, including immune response (IFI6 [49], CX3CR1 [50], USP18 [51],…”

“…In contrast, seven genes (MAFF, HSPB8, BAG3, TAGLN, POPDC2, SCN1B, and NT5C1A) were commonly upregulated in wild boars (206 genes) and red junglefowl (200 genes). The upregulated genes in the domesticated animals were involved in various biological processes, including immune response (IFI6 [49], CX3CR1[50], USP18[51], CXCL13[52], PHF11[53], CMPK2[54]), olfactory learning (PRTFDC1[55]), epigenetic regulation (EZH2[56]), cell division (CEP20[57]), and extracellular matrix (NID1[58]). These changes in gene expression may contribute to the adaptation of the immune system, changes in olfaction, regulation of growth and development, and morphological changes associated with domestication.…”