Host genetic susceptibility to viral infections: the role of type I interferon induction

Abstract

The innate immune response is the major front line of defense against viral infections. It involves hundreds of genes with antiviral properties which expression is induced by type I interferons (IFNs) and are therefore called interferon stimulated genes (ISGs). Type I IFNs are produced after viral recognition by pathogen recognition receptors, which trigger a cascade of activation events. Human and mouse studies have shown that defective type I IFNs induction may hamper the ability to control viral infections. In humans, moderate to high-effect variants have been identified in individuals with particularly severe complications following viral infection. In mice, functional studies using knockout alleles have revealed the specific role of most genes of the IFN pathway. Here, we review the role of the molecular partners of the type I IFNs induction pathway and their implication in the control of viral infections and of their complications.

Identifying potential novel insights for COVID-19 pathogenesis and therapeutics using an integrated bioinformatics analysis of host transcriptome

“…MYLK, in module 4, is found to be downregulated, and its role in the pathogenesis of COVID-2 is unclear. Besides, Genes of module 5 (MX2, IFI27, and GBP5) were upregulated and highlighted the role of type I interferon signaling pathway and innate immune response in COVID-19 pathogenesis [2] , [71] , [72] , [73] . SARS-CoV-2-infection upregulated genes (TGM1, SPRR1B, LOR, SPRR2E, SPRR2D, SPRR1A, IVL, FLG, and SPRR2A) involved in cornification and peptide cross-linking, which were enriched for module 6.…”

Identifying potential novel insights for COVID-19 pathogenesis and therapeutics using an integrated bioinformatics analysis of host transcriptome

“…Besides, Genes of module 5 (MX2, IFI27, and GBP5) were upregulated and highlighted the role of type I interferon signaling pathway and innate immune response in COVID-19 pathogenesis [2,[59][60][61]. SARS-CoV-2-infection up-regulated genes (TGM1, SPRR1B, LOR, SPRR2E, SPRR2D, SPRR1A, IVL, FLG, and SPRR2A) involved in cornification and peptide cross-linking which were enriched for module 6, this may lead to cell death and involved in lung fibrosis respectively [62][63][64].…”

The Role of Immunogenetics in COVID-19

“…Synthesis and release of type I interferons together with their signaling by binding to IFN-α receptor 1 (IFNAR1) and IFNAR2 are all fundamental steps in the defense process raised by viral RNA or DNA. These molecular pathways involve a number of actors, including toll like receptors (TLR), IFN regulatory factors (IRF), signal transducers and activator of transcription (STAT) 1 and 2, TIR-domain containing adaptor inducing IFN-β (TICAM1/TRIF), TANK binding kinase 1 (TBK10), TNF Receptor Associated Factor 3 (TRAF3) and Unc-93 homolog B1 (UNC93B1) [101][102][103][104][105][106][107][108][109][110][111][112].…”