Genetic characteristics and polymorphisms in the chicken interferon-induced transmembrane protein (IFITM3) gene

Abstract

The interferon-induced transmembrane protein 3 (IFITM3) gene is classified as a small interferon-stimulated gene and is associated with a broad spectrum of antiviral functions against several fatal enveloped viruses, including influenza A viruses (IAVs). The rs12252 single nucleotide polymorphism (SNP) of the IFITM3 gene in humans was associated with susceptibility to H1N1 influenza in a 2009 pandemic. In addition, overexpression of the IFITM3 protein potently inhibits the highly pathogenic avian influenza H5N1 virus in ducks and chickens. Although chickens are a major host of influenza viruses and the IFITM3 gene participates in the host antiviral system, studies on chicken IFITM3 gene are very rare. To investigate the genetic characteristics of the chicken IFITM3 gene, we performed direct sequencing and alignment in 108 Dekalb White and 72 Ross breeds. We also investigated the genotype and haplotype frequencies and linkage disequilibrium of the IFITM3 gene polymorphisms and evaluated whether the non-synonymous SNPs are deleterious. We found significantly different genotype, allele and haplotypes frequencies between two chicken breeds, Dekalb White and Ross. Furthermore, we compared and analyzed the promoter structure of the chicken IFITM3 gene with that of several species. We found that birds have a long C-terminal domain and inverted topology of the IFITM3 protein compared to mammals. We also identified fourteen genetic polymorphisms in the chicken IFITM3 gene. L100 M and N125H were predicted as 'probably damaging' and L100 M can alter the length of its conserved intracellular loop (CIL). Furthermore, chickens, but not mammals, contain CpG islands (CGIs) in this promoter region.

Role of the Host Genetic Susceptibility to 2009 Pandemic Influenza A H1N1

“…All of the IFITM genes contain two exons in their structure. The interferon-induced transmembrane protein 3 ( IFITM3 ) gene is an endogenous immune-related gene considered as a small ISGs, since it includes an interferon-stimulated response element (ISRE) in its promoter region, which promotes a robustly up-regulated expression of IFITM3 by the stimulus of all three types IFNs, resulting in a significant affinity of transcriptional factors, the most critical being POLR2A , MYC , ELF1 , PHF8 , CHD1 , TAF1 , REST , SIN3AK20 , SIN3A , IRF1 , STAT1 , TBP , STAT3 , STAT2 , ZBTB7A , and CTCF [ 43 , 44 , 45 , 46 ].…”

Genetic association between the rs12252 SNP of the interferon-induced transmembrane protein gene and influenza A virus infection in the Korean population

“…Interferon-induced transmembrane protein 3 (IFITM3) is a host antiviral effector protein that augments expression levels by type I and II interferons to respond to the invasion of various viruses, including influenza A virus (IAV) (Brass et al 2009 ; Weidner et al 2010 ; Bailey et al 2012 ; Diamond and Farzan 2013 ; Kim et al 2019 ; Lee et al 2019 ). IFITM3 protein is localized in late endosomes and inhibits endosomal escape of influenza A viruses (Feeley et al 2011 ).…”

Ethnic variation in risk genotypes based on single nucleotide polymorphisms (SNPs) of the interferon-inducible transmembrane 3 (IFITM3) gene, a susceptibility factor for pandemic 2009 H1N1 influenza A virus

“…A recent study reported a difference in the expression level of IFITM3 protein between avian influenza-susceptible animals and avian influenza-resistant animals (Smith et al 2015 ). In addition, a difference in the genetic distribution of polymorphisms of the chicken IFITM3 gene was also identified between layers and broilers, which are bred for eggs and meats, respectively (Kim et al 2019 , 2020 ). Furthermore, since pig IFITM3 protein showed a defensive capacity against classical swine fever virus (CSFV), African swine fever virus (ASFV), and foot and mouth disease virus (FMDV), further investigation of the polymorphisms of animal IFITM3 genes is needed in the future (Li et al 2019 ; Munoz-Moreno et al 2016 ; Xu et al 2014 ).…”