Abstract
RIG-I and MDA5 are two key pattern recognition receptors that sense RNA virus invasion, but RIG-I is absent in chickens. Although chickens have intact MDA5, the genes downstream of chicken MDA5 (chMDA5) that may mediate antiviral response are not well studied. We compared the transcriptional profile of chicken embryonic fibroblasts (DF1) transfected with chMDA5, and poly(I:C), using RNA-seq. Transfected chMDA5 and poly(I:C) in DF1 cells were associated with the marked induction of many antiviral innate immune genes compared with control. Interestingly, nine interferon-stimulated genes (ISGs) were listed in the top 15 upregulated genes by chMDA5 and poly(I:C) transfection. We used real-time PCR to confirm the upregulation of the nine ISGs, namely, MX1, IFI6, IFIT5, RSAD2, OASL, CMPK2, HELZ2, EPSTI1, and OLFML1, by chMDA5 and poly(I:C) transfection in DF1 cells. However, avian influenza virus H5N6 infection only increased MX1, IFI6, IFIT5, RSAD2, and OASL expression levels. Further study showed that the overexpression of these five genes could significantly inhibit H5N6 virus replication. These results provide some insights into the gene expression pattern induced by chMDA5, which would be beneficial for understanding and identifying innate immune genes of chicken that may lead to new antiviral therapies.
Highlights
The recognition of viruses by host cells is mediated by pattern recognition receptors (PRR) sensing virus-specific pathogen-associated nucleic acids
We demonstrated that several interferon-stimulated genes (ISGs) that were mostly regulated by chicken MDA5 (chMDA5) could significantly inhibit avian influenza virus (AIV) H5N6 infection
We found that STAT1 and STAT2 were significantly increased by chMDA5 transfection, which could lead to the increased expression of ISGs
Summary
The recognition of viruses by host cells is mediated by pattern recognition receptors (PRR) sensing virus-specific pathogen-associated nucleic acids. PRR activation leads to the induction of type I interferon (IFN), cytokine secretion, and the activation of antigen presenting cells promoting adaptive immune responses [1,2]. PRRs consist of four main categories: the retinoic acid-inducible gene I (RIG-I)-like receptors (RLR), the Toll-like receptors, the NOD-like receptor, and C-type lectin receptors. RLRs are ubiquitously expressed in the cytoplasm and comprise RIG-I, MDA5, and LGP2. RIG-I and MDA5 contain two N-terminal caspase activation and recruitment (CARD) domains [3] and a. The interaction of CARDs activates the downstream signaling cascade, which results in the expression of type I IFNs. The interaction of CARDs activates the downstream signaling cascade, which results in the expression of type I IFNs
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