interferons are a group of immune system signalling proteins belonging to the group of
cytokines, named as they “interfere” with viral replication and were first described in 1957
in general, type I and II interferons are responsible for regulating and activating the immune response, in particular to viral infections, while type III interferons have important roles in both viral and fungal infections
IFNs activate signal transducer and activator of transcription (STAT) complexes which regulate the expression of certain immune system genes - each IFN type can activate unique STATs in addition to shared STATs, and STATs then activate the Janus kinase-STAT (JAK-STAT) signaling pathway
they can inhibit intracellular viral replication via:
reduction of protein synthesis in the cell via stimulating production of large amounts of protein kinase R (PKR)
increases destruction of intracellular RNA via stimulating production of RNAse L enzyme
inducing production of hundreds of other proteins—known collectively as interferon-stimulated genes (ISGs)
they can limit viral spread via increasing p53 activity, which kills virus-infected cells by promoting apoptosis
they can increase the expression of major histocompatibility complex (MHC) antigens and improve host immune responses by increasing antigen presentation
they can activate natural killer cells and macrophages
along with other cytokines, they are responsible for the viraemic symptoms of fever, myalgias, etc
virtually all cell types can express type I and III interferons in response to viral infection of the cell, triggers include:
pattern recognition receptors, such as membrane bound toll like receptors or the cytoplasmic receptors RIG-I or MDA5 detecting:
viral glycoproteins, viral RNA, bacterial endotoxin (lipopolysaccharide), bacterial flagella, and CpG motifs
Toll Like Receptor 3 (TLR3) can detect viral dsRNA which can then activate the transcription factors IRF3 and NF-κB which are important for initiating synthesis of many inflammatory proteins.
type II interferons are generally only produced by immune cells
many viruses have found ways to reduce actions of interferons and thus cause infection such as by:
produce proteins that bind to IFNs and thus stop them binding to receptors
inhibition of IFN signaling
prevention of further IFN production
inhibition of proteins produced by actions of IFNs
etc