Peginterferon alfa-2a is a modified form of recombinant human interferon, which is used to activate interferon alpha receptors in the JAK-STAT pathway. This is used to stimulate the innate antiviral response in the treatment of hepatitis B and C viruses. Peginterferon alfa-2a activate interferon alpha receptors 1 and 2 (IFNAR1 and IFNAR2) which are associated with tyrosine kinase 2 (TYK2) and JAK1 respectively. This receptor complex also phosphorylates STAT3 homodimers. The IFNAR complex phorphoylates STAT5 which binds with Crk-like protein (CRKL). This activates the transcription of gamma activated sequence (GAS) elements, which activates an inflammatory response and immunoregulation. The main pathway of IFNAR1 and IFNAR2 is through the phosphorylation of STAT1 and STAT2. Together with interferon regulatory factor (IRF9) they form the interferon-stimulated gene factor 3 (ISGF3). The ISGF3 translocates to the nucleus and initiates the trascription of Interferon-sensitive response element (ISRE). This leads to an antiviral response, immunoregulation, antigen presentation, and checkpoint proteins. THE ISRE genes also activate IFN regulated genes. These along with lipopolysaccharides or foreign pathogens activates interferon Regulatory Factor 7 (IRF7). IRF7 is phosphorylated and bound with nuclear factor kappa B (NFKB). This causes the induction of type 1 INFs, which further activates the pathway. IFNAR1 and IFNAR2 signal through TYK2 and JAK1 to also trigger the activation of the NFKB pathway through phosphorylated STAT3, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and TNF receptor-associated factors (TRAFs). They act through IKKa and IKKb to drive NFKB induction of genes associated with survival signals, antigen processing and presentation, and proliferation.

Peginterferon alfa-2a Pathway References