The Characterization of chIFITMs in Avian Coronavirus Infection In Vivo, Ex Vivo and In Vitro

Abstract

The coronaviruses are a large family of enveloped RNA viruses that commonly cause gastrointestinal or respiratory illnesses in the infected host. Avian coronavirus infectious bronchitis virus (IBV) is a highly contagious respiratory pathogen of chickens that can affect the kidneys and reproductive systems resulting in bird mortality and decreased reproductivity. The interferon-inducible transmembrane (IFITM) proteins are activated in response to viral infections and represent a class of cellular restriction factors that restrict the replication of many viral pathogens. Here, we characterize the relative mRNA expression of the chicken IFITM genes in response to IBV infection, in vivo, ex vivo and in vitro using the pathogenic M41-CK strain, the nephropathogenic QX strain and the nonpathogenic Beaudette strain. In vivo we demonstrate a significant upregulation of chIFITM1, 2, 3 and 5 in M41-CK- and QX-infected trachea two days post-infection. In vitro infection with Beaudette, M41-CK and QX results in a significant upregulation of chIFITM1, 2 and 3 at 24 h post-infection. We confirmed a differential innate response following infection with distinct IBV strains and believe that our data provide new insights into the possible role of chIFITMs in early IBV infection.

In Vitro Characterization of chIFITMs of Aseel and Kadaknath Chicken Breeds against Newcastle Disease Virus Infection

“…While CEF cells from Aseel took longer to exhibit strong mRNA expression of the chIFN-γ and chIFITM genes, they were strongly expressed at 6 h post-infection. In Kadaknath CEF, among the IR-IFITM family members, chIFITM3 (11.68 log 2 folds) has the greatest expression observed at 6 h post-infection, followed by chIFITM2 (8.89 log 2 folds) at 48 h post-infection, chIFITM1 (7.79 log 2 folds), and chIFITM5 (7.04 log 2 folds) at 24 h post-infection [14,16]. However, in Aseel, IFITM1 (6.00 log 2 folds) came first, then chIFITM3 (3.46 log 2 folds), then chI-FITM2 (3.25 log 2 folds) at 6hpi, and lastly chIFITM5 (3.82 log 2 folds) at 24 hpi.…”

“…Chicken has five members of the IFITM family: chIFITM1, chIFITM2, chIFITM3, chIFITM5, and chIFITM10. These protein genes are activated and made to express themselves by type I and type II IFNs, signifying the start of the innate host response in a negative feedback manner [14,33,34]. Recent studies confirm that STAT/IRF signaling pathways activate IFITM gene expression together with other ISGs during infection and inflammation [35].…”

“…Scientists discovered that chIFITM gene expression has a negative correlation with the emergence of the influenza virus and its titre in vitro, indicating that chIFITMs 1,2, and 3 have a functional role in the management of viral infections [12,13]. In chickens, IFITM genes were located in Chromosome 5 and found in two loci, one containing the various numbers of immune-related (IR)-IFITM (IFITM1, 2, and 3) genes, and the IFITM5 gene and the IFITM10 gene in another locus [14,15]. Lanzet al found that swIFITMs (swine IFITMs) had a dose-dependent restriction against IAV after infecting porcine HEK293-T cells with IAV A/WSN/33 (WSN) for 24 or 48 h [16].…”

Host Immune Response Modulation in Avian Coronavirus Infection: Tracheal Transcriptome Profiling In Vitro and In Vivo

“…Tracheal organ culture has long been used to investigate IBV infection [ 106 , 107 , 108 , 109 , 110 , 111 , 112 ]. While this ex vivo model offers many benefits, understanding the mechanisms specifically at the level of tracheal epithelial cells is useful for studying immediate host responses under highly controlled conditions.…”

Chicken interferon-induced transmembrane protein 1 promotes replication of coronavirus infectious bronchitis virus in a cell-specific manner

“…Transgenic chicks expressing ifitm1 have been demonstrated to restrict H5N1 influenza viruses ( Rohaim et al, 2021 ). Recent studies have demonstrated that infection with IBV will increase the expression of IFITMs in chicks ( Steyn et al, 2020 ).…”