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Overexpression of chicken IRF7 increased viral replication and programmed cell death to the avian influenza virus infection through TGF-beta/FoxO signaling axis in DF-1

ABSTRACT: To elucidate the functional role of chicken IRF7 against avian influenza virus (AIV) infection, we generated inducible IRF7 overexpression DF-1 cell lines that could fine control the IRF7 expression level and performed in vitro infection using low pathogenic AIVs (LPAIVs) followed by RNA-seq.

ORGANISM(S): Gallus gallus

PROVIDER: GSE115131 | GEO | 2018/06/01

REPOSITORIES: GEO

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Chicken IRF7 knockout by CRISPR-Cas9 in DF-1 and in vitro H6N2 infection followed by RNA-seq

Project description:To elucidate the functional role of chicken IRF7 against avian influenza virus (AIV) infection, we generated inducible IRF7 knockout DF-1 cell lines and performed in vitro infection using low pathogenic AIVs (LPAIVs) followed by RNA-seq.

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Genome-wide profiling of microRNAs revealing novel insights into mutual interactions mechanism between H9N2 avian influenza virus and avian dendritic cells

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Project description:Avian influenza caused significant damages to the poultry industry, efforts have been made to reveal the disease mechanisms as well as mechanisms of disease resistance. Here, by investigating two chicken breeds with distinct responses to avian influenza virus (AIV), Leghorn GB2 and Fayoumi M43, we compared their differences in genome, methylation and transcriptome. Except for MX1 involved direct acting antiviral mechanism, we found that in both methylation and transcriptome levels the more AIV resistant breed Fayoumi showed less variations compared to White Leghorn after AIV challenging. Fayoumi also showed better consistency between the changes in methylation and changes in transcriptome level. Our results suggested a homeostasis hypothesis of avian influenza resistance, with Fayoumi better maintaining homeostasis both in epigenetic and gene expression levels.

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Overexpression of Chicken IRF7 Increased Viral Replication and Programmed Cell Death to the Avian Influenza Virus Infection Through TGF-Beta/FoxO Signaling Axis in DF-1.

Project description:During mammalian viral infections, interferon regulatory factor 7 (IRF7) partners with IRF3 to regulate the type I interferon response. In chickens, however, it is still unclear how IRF7 functions in the host innate immune response, especially given that IRF3 is absent. To further elucidate the functional role of chicken IRF7 during avian influenza virus (AIV) infection, we generated inducible IRF7 overexpression DF-1 cell lines and performed in vitro infection using low pathogenic AIVs (LPAIVs). Overexpression of IRF7 resulted in higher viral replication of H6N2 and H10N7 LPAIVs compared to empty vector control cells regardless of IRF7 expression level. In addition, a high rate of induced cell death was observed due to elevated level of IRF7 upon viral infection. RNA-seq and subsequent transcriptome analysis of IRF7 overexpression and control cells discovered candidate genes possibly controlled by chicken IRF7. Functional annotation revealed potential pathways modulated by IRF7 such as TGF-beta signaling pathway, FoxO signaling pathway and cell structural integrity related pathways. Next, we analyzed the host response alteration due to the IRF7 overexpression and additionally discovered the possible connection of chicken IRF7 and JAK-STAT signaling pathway. These findings suggest that chicken IRF7 could modulate a wide range of cellular processes in the host innate immune response thus meticulous control of IRF7 expression is crucial to the host in response to AIV infection.

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