Interferon regulatory factor 7- (IRF7-) mediated immune response affects Newcastle disease virus replication in chicken embryo fibroblasts

Abstract

Interferon regulatory factor 7 (IRF7) is essential for the induction of an antiviral response. Previous studies have shown that virus replication causes the activation or expression of Type I interferon (IFN) in cells, which further activates IFN-stimulated genes (ISGs) to retard virus growth. In this study, after infection of chicken embryo fibroblasts (CEFs) with the lentogenic Newcastle disease virus (NDV) strain LaSota or the velogenic NDV strain GM, the mRNA and protein levels of IRF7 showed a significant increase, and part of the IRF7 protein was translocated from the cytoplasm to the nucleus. In order to further explore the effect of IRF7-mediated innate immune response on the replication of NDV in CEFs, the mRNA levels of IFN-α, IFN-β and STAT1 were measured and the replication kinetics of NDV determined. The results showed that specific siRNA could inhibit the expression of IRF7 and limit the mRNA level of IFN-α, IFN-β and STAT1 and, accordingly, the replication kinetics of both NDVs were enhanced after the inhibition of IRF7. In conclusion, IRF7 is an important nuclear transcription factor for the induction of Type I IFNs during the antiviral response, which can affect the replication of NDV and spread to CEFs in the early phase of viral infection.

Newcastle disease virus RNA-induced IL-1β expression via the NLRP3/caspase-1 inflammasome

“…Specifically, IL-1β was highly expressed in the lungs and glandular stomach, which are important target organs of NDV, in chickens infected with the virulent strain compared to those infected with the attenuated virus. Moreover, when infected at a MOI of 1, GM NDV induced higher levels of IL-1β than those induced by the La Sota virus in a time-dependent manner, which is consistent with the results of previous studies [47]. Furthermore, as previously noted, treatment of chickens with anti-IL-1β antibodies following infection with GM NDV decreased IL-1β level in organs, reduced body temperature and decreased the mortality rate, further confirming an essential role for IL-1β in the virulence of NDV infection.…”

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

“…The expressions of crucial genes, including TLR3, TLR7, IL1B, IRF7, IL8, STAT1, and MHC class I and II molecules, are characteristic of NDV infection in chicken cells. However, in previously performed studies, a significant expression of type I IFNs (INF-α and IFN-β) was observed against NDV infection [53,54]. Surprisingly, in our experimental settings, we were unable to observe this response.…”

“…Major genes including IL1β, IL6, IL8, CCL4, CCL5, STAT1, TLR3, IRF7, IFITM-1, IFITM-3, IFITM-5, STAT1, NF-kB, MX1, RSAD2 (viperin), MDA5, and ZAP were identified in this study ( Supplementary Table S1). Interestingly, among all those crucial genes related to innate immunity identified in the present study, we found that TLR3, TLR7, IL1B, IRF7, IL8, STAT1, and MHC class I and II molecules are exactly the same as those observed in previously studies where similar gene expression was shown in CEFs treated with NDV (genotype VII and IX) [53,54]. In short, our results demonstrated a low level (nonsignificant) expression of IFN-α and IFN-β.…”

Knockout of IRF7 Highlights its Modulator Function of Host Response Against Avian Influenza Virus and the Involvement of MAPK and TOR Signaling Pathways in Chicken

“…In our previous study using stable IRF7 overexpression and knockdown in chicken DF-1 cell lines with double-stranded RNA (dsRNA) analog poly(I:C) (polyinosinic-polycytidylic acid) inductions, we demonstrated the conserved function of IRF7 as a type I IFN modulator [14]. Another study also suggested a similar role of IRF7 by the siRNA knockdown of IRF7 in chicken embryonic fibroblasts (CEFs), which limited IFNA, IFNB and STAT1 (signal transducer and activator of transcription 1) expression and increased Newcastle disease virus replication [15]. While these knockdown approaches such as RNA interference (RNAi) have successfully generated partial IRF7 loss-of-function phenotypes in chickens, and generated some novel insights into the role of IRF7 in the regulation of the host response to virus infection in poultry, RNAi has its own technical limitation of incompleteness of knockouts [16].…”