Antiviral Activity of Lambda Interferon in Chickens

Reuter, Antje; Soubies, Sébastien Mathieu; Härtle, Sonja; Schusser, Benjamin; Kaspers, Bernd; Staeheli, Peter; Rubbenstroth, Dennis

doi:10.1128/jvi.02764-13

Cited by 62 publications

(71 citation statements)

References 30 publications

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“…IFN and IFN play an important role in guarding avian species against viral infections including NDV (Reuter et al 2014). This study revealed that MG down regulated the IFNá and IFNã gene expression, facilitating the NDV infection by suppressing the antiviral immune response in co-infected birds as compared to birds infected only with NDV.…”

Section: Serological Examinationmentioning

confidence: 84%

Mycoplasma gallisepticum modifies virus shedding and immune response of Newcastle disease virus in broilers

Qamar-un-Nisa

Younus

Khan

et al. 2017

IJAR

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Respiratory diseases are responsible for major economic losses in poultry farms. Newcastle disease virus (NDV) infections cause huge economic losses in poultry industry especially in the presence of other co-infecting pathogens. The purpose of this study was to assess the less understood effect of Mycoplasma gallisepticum (MG) on the replication and immune responses of NDV in broiler chicken. Three-week-old commercial broiler chickens were inoculated with either NDV, MG or both etiological agents. The experimental groups were identified as follows: negative control (Group C), Mycoplasma challenged (Group M), NDV challenged (Group V) and virus and Mycoplasma challenged (Group V+M). Blood samples and swabs were collected on daily basis for two weeks. All infected birds showed positive results for NDV shedding, however, the pattern of virus shedding was different, with birds of the group V+M showing more pronounced virus shedding than the birds in the group V. In addition, birds of V+M group showed significant reduction in anti-AI antibody responses and interferon gene expression than the birds in the V group. The present study revealed that MG could facilitate replication of NDV by bringing alterations in immune responses.

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Section: Serological Examinationmentioning

confidence: 84%

Mycoplasma gallisepticum modifies virus shedding and immune response of Newcastle disease virus in broilers

Qamar-un-Nisa

Younus

Khan

et al. 2017

IJAR

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“…Intriguingly, chIFN-λ activated a weaker chMx promoter activity in established chicken fibroblasts (Figure 1A). Since all three types of IFNs activate JAK-STAT pathway in a receptor-specific manner, it has been revealed that DF-1 cell line showed suppressed expression of chIL28Rα receptor [28], which led to attenuated promoter activities. Moreover, we demonstrated a suppressive response of DF1 against chIFN-λ in an IFN-bioassay.…”

Section: Resultsmentioning

confidence: 99%

“…Building upon existing information on chicken ISGs [18,30,32] and our recent studies [3, 33], we compared the expression of the genes, which are induced by either chIFN-α, chIFN-λ or chIFN-γ and catalogue the genes which are IFN-specific or genes that are shared between different types of IFNs in chicken. Since IFNs show cell and tissue-specific actions [8], which are mainly attributed to their cognate expression patterns [28], we attempted to establish a model system that could reliably respond to all type of IFNs. The chicken fibroblast (DF-1), one of the most characterized cell lines in avian research, was selected.…”

Section: Discussionmentioning

confidence: 99%

“…The chicken fibroblast (DF-1), one of the most characterized cell lines in avian research, was selected. However, due to repressive expression of chIFN-λ receptors [28], the treatment of DF1 with type III IFN showed defective genes inductions, IFN-promoter activation and cumulatively established an antiviral state against IFN-sensitive virus (VSV). We thus exploited a permanent DF1 cell line that exogenously express chIFN-λ receptors and thus revised the full responsiveness to type III as well as other IFNs.…”

Section: Discussionmentioning

confidence: 99%

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Genome-Wide Classification of Type I, Type II and Type III Interferon-Stimulated Genes in Chicken Fibroblasts

Santhakumar

Rohaim

Munir

2019

Preprint

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Interferons (IFNs) play central roles in establishing innate immunity and mediating 12 adaptive immunity against multiple pathogens. Three known types of IFNs identify their cognate 13 receptors, initiate cascades of signalling events and eventually result in the induction of myriad of 14 IFN-stimulated genes (ISGs). These ISGs perform multitude of functions and cumulatively 15 corroborate a bespoke antiviral state to safeguard hosts against invading viruses. Owing to unique 16 nature of chicken's immune system and lack of foundational profiling information on the nature and 17 dynamic expression of IFN-specific ISGs at the genome scale, we performed a systematic and 18 extensive analysis of type I, II and III IFN-induced genes in chicken. Employing pan-IFN responsive 19 chicken fibroblasts coupled with transcriptomics we observed an overwhelming over-representation 20 of up-regulated ISGs by all types of IFNs. Intriguingly, prediction of IFN-stimulated response element 21(ISRE) and gamma-IFN activation sequence (GAS) revealed a substantial number of GAS motifs in 22 selective significantly induced ISGs in chicken. Extensive comparative, genome-wide and differential 23 expression analysis of ISGs under equivalent signalling input catalogue a set of genes that were 24 either IFN-specific or independent of types of IFNs used to prime fibroblasts. These comprehensive 25 datasets, first of their kinds in chicken, will establish foundations to elucidate the mechanisms of 26 actions and breadth of antiviral action of ISGs which may propose alternative avenues for the 27 targeted antiviral therapy against viruses of poultry and public health importance.28 29 30 31 32 33 34 35 36 37 65 and Janus Kinase 1 (JAK1). However, type II IFN triggers this pathway via the activation of STAT1 66 homodimers mediated by JAK1 and JAK2 kinases [4]. 68Mammalian type I and type III IFNs signal through the JAK-STAT pathway to activate the 69 heterotrimeric interferon-stimulated gene factor 3 (ISGF3) complex, comprised of phosphorylated 70 STAT1 and STAT2, and interferon regulatory factor 9 (IRF9) [7,8] (yet to be identified in chickens). In 71 contrast, type II IFNs initiate the formation of a STAT1-STAT1 homodimer to assemble GAF, without 72 the need of IRF9. Upon nuclear translocation, ISGF3 and gamma-interferon activation factor (GAF) 73 bind to IFN-stimulated response elements (ISREs) [6] or gamma-IFN activation sequence (GAS) 74 motifs, respectively 7 leading to the transcriptional activation of hundreds of ISGs which encode 75 proteins that act via a variety of mechanisms to restrict viral infection [9-11]. 77It has been demonstrated that JAK-STAT pathway initiates transcriptional regulation of a string of 78 cytokines, chemokine, antimicrobial products and regulators of apoptotic pathways [2,7]. In 79 mammals, a range of genome scale transcriptomics screening approaches has been applied to map 80 the diversity, kinetics and expression patterns of these antiviral factors. Based on these data, recent 81 studies have applied large-sc...

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“…Administration of chIFN-γ along with fowlpox and DNA vaccines resulted in elevated antibody titer, improved cellular responses, and protection against NDV challenge in chickens and turkeys [25,34,35]. Similarly, chicken embryo fibroblasts (CEFs) do not have the key receptors required for type III IFNs (IFN-λ) [36]. Therefore, we explored the potential of IFN-γ to act against NDV in CEFs, in vitro.…”

Section: Introductionmentioning

confidence: 99%

IFN-γ establishes interferon-stimulated gene-mediated antiviral state against Newcastle disease virus in chicken fibroblasts

Yang¹,

Mehboob²,

Liu³

et al. 2020

ABBS

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Newcastle disease virus (NDV) causes severe economic losses through severe morbidity and mortality and poses a significant threat to the global poultry industry. Significant efforts have been made to develop novel vaccines and therapeutics; however, the interaction of NDV with the host is not yet fully understood. Interferons (IFNs), an integral component of innate immune signaling, act as the first line of defense against invading viruses. Compared with the mammalian repertoire of IFNs, limited information is available on the antiviral potential of IFNs in chickens. Here, we expressed chicken IFN-γ (chIFN-γ) using a baculovirus expression vector system, characterized its antiviral potential against NDV, and determined its antiviral potential. Priming of chicken embryo fibroblasts with chIFN-γ elicited an antiviral environment in primary cells, which was mainly due to interferon-stimulated genes (ISGs). A genome-wide transcriptomics approach was used to elucidate the possible signaling pathways associated with IFN-γ-induced immune responses. RNAsequencing (RNA-seq) data revealed significant induction of ISG-associated pathways, activated temporal expression of ISGs, antiviral mediators, and transcriptional regulators in a cascade of antiviral responses. Collectively, we found that IFN-γ significantly elicited an antiviral response against NDV infection. These data provide a foundation for chIFN-γ-mediated antiviral responses and underpin functional annotation of these important chIFN-γ-induced antiviral influencers.

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Antiviral Activity of Lambda Interferon in Chickens

Cited by 62 publications

References 30 publications

Mycoplasma gallisepticum modifies virus shedding and immune response of Newcastle disease virus in broilers

Mycoplasma gallisepticum modifies virus shedding and immune response of Newcastle disease virus in broilers

Genome-Wide Classification of Type I, Type II and Type III Interferon-Stimulated Genes in Chicken Fibroblasts

IFN-γ establishes interferon-stimulated gene-mediated antiviral state against Newcastle disease virus in chicken fibroblasts

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Antiviral Activity of Lambda Interferon in Chickens

Cited by 62 publications

References 30 publications

Mycoplasma gallisepticum modifies virus shedding and immune response of Newcastle disease virus in broilers

Mycoplasma gallisepticum modifies virus shedding and immune response of Newcastle disease virus in broilers

Genome-Wide Classification of Type I, Type II and Type III Interferon-Stimulated Genes in Chicken Fibroblasts

IFN-&gamma; establishes interferon-stimulated gene-mediated antiviral state against Newcastle disease virus in chicken fibroblasts

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IFN-γ establishes interferon-stimulated gene-mediated antiviral state against Newcastle disease virus in chicken fibroblasts