Final published version
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Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Genome-wide classification of type I, type II and type III interferon-stimulated genes in chicken fibroblasts
AU - Santhakumar, D.
AU - Rohaim, M.A.
AU - Munir, M.
PY - 2019/10/25
Y1 - 2019/10/25
N2 - Interferons (IFNs) play central roles in establishing innate immunity and mediating adaptive immunity against multiple pathogens. Three known types of IFNs identify their cognate receptors, initiate cascades of signalling events and eventually result in the induction of a myriad of IFN-stimulated genes (ISGs). These ISGs perform a multitude of functions and cumulatively corroborate a bespoke antiviral state to safeguard hosts against invading viruses. Owing to the unique nature of a chicken’s immune system and the lack of foundational profiling information on the nature and dynamic expression of IFN-specific ISGs at the genome scale, we performed a systematic and extensive analysis of type I, II and III IFN-induced genes in chicken. Employing pan-IFN responsive chicken fibroblasts coupled with transcriptomics, we observed an over-representation of up-regulated ISGs compared to down-regulated ISGs by all types of IFNs. Intriguingly, prediction of IFN-stimulated response element (ISRE) and gamma-IFN activation sequence (GAS) revealed a substantial number of GAS motifs in selective and significantly induced ISGs in chicken. Extensive comparative, genome-wide and differential expression analysis of ISGs under equivalent signalling input catalogue a set of genes that were either IFN-specific or independent of types of IFNs used to prime fibroblasts. These comprehensive datasets, first of their kinds in chicken, will establish foundations to elucidate the mechanisms of actions and breadth of antiviral action of ISGs, which may propose alternative avenues for targeted antiviral therapy against viruses of poultry of public health importance.
AB - Interferons (IFNs) play central roles in establishing innate immunity and mediating adaptive immunity against multiple pathogens. Three known types of IFNs identify their cognate receptors, initiate cascades of signalling events and eventually result in the induction of a myriad of IFN-stimulated genes (ISGs). These ISGs perform a multitude of functions and cumulatively corroborate a bespoke antiviral state to safeguard hosts against invading viruses. Owing to the unique nature of a chicken’s immune system and the lack of foundational profiling information on the nature and dynamic expression of IFN-specific ISGs at the genome scale, we performed a systematic and extensive analysis of type I, II and III IFN-induced genes in chicken. Employing pan-IFN responsive chicken fibroblasts coupled with transcriptomics, we observed an over-representation of up-regulated ISGs compared to down-regulated ISGs by all types of IFNs. Intriguingly, prediction of IFN-stimulated response element (ISRE) and gamma-IFN activation sequence (GAS) revealed a substantial number of GAS motifs in selective and significantly induced ISGs in chicken. Extensive comparative, genome-wide and differential expression analysis of ISGs under equivalent signalling input catalogue a set of genes that were either IFN-specific or independent of types of IFNs used to prime fibroblasts. These comprehensive datasets, first of their kinds in chicken, will establish foundations to elucidate the mechanisms of actions and breadth of antiviral action of ISGs, which may propose alternative avenues for targeted antiviral therapy against viruses of poultry of public health importance.
KW - interferons
KW - chicken
KW - birds
KW - innate immunity
KW - ISGs
KW - IFN-regulated genes
KW - immunity
U2 - 10.3390/vaccines7040160
DO - 10.3390/vaccines7040160
M3 - Journal article
VL - 7
JO - Vaccines
JF - Vaccines
IS - 4
M1 - 160
ER -