Peptidyl-prolyl cis-trans isomerase A (Cyclophilin A)–Interferon regulatory factor 9 (IRF9) interface (CypA–IRF9 interface)

The Peptidyl-prolyl cis-trans isomerase A (Cyclophilin A)–Interferon regulatory factor 9 (IRF9) interface is a critical protein-protein interaction (PPI) that regulates the innate immune response, specifically the Type I and Type III interferon (IFN) signaling pathways. Peptidyl-prolyl cis-trans isomerase A, commonly known as Cyclophilin A, acts as a molecular chaperone that binds to Interferon regulatory factor 9 to facilitate its stability and promote its translocation into the nucleus upon IFN stimulation (Sun et al., 2014, Journal of Virology). Within the nucleus, Interferon regulatory factor 9 is a vital component of the ISGF3 complex, which drives the transcription of interferon-stimulated genes (ISGs) necessary for an effective antiviral response (UniProt P62937, Q00610). While Peptidyl-prolyl cis-trans isomerase A is frequently hijacked by viruses such as Hepatitis C (HCV) and HIV-1 to assist in their replication cycles, its interaction with Interferon regulatory factor 9 is a key component of the host's own defense mechanism (PubMed 24501000). Drugs that target Peptidyl-prolyl cis-trans isomerase A, such as the immunosuppressant Cyclosporine A and non-immunosuppressive analogs like Alisporivir, disrupt this interface, thereby modulating the cellular antiviral state and IFN-mediated gene expression (NIH/PubChem). Targeting this specific PPI is of therapeutic interest for treating chronic viral infections and autoimmune conditions where interferon signaling is pathologically elevated.

Other names

Cyclophilin A–IRF9 interfacePPIA–IRF9 interactionCyclophilin A–IRF9 complexCypA–IRF9 protein-protein interaction

Inhibition of the protein-protein interaction between Peptidyl-prolyl cis-trans isomerase A and Interferon regulatory factor 9, which prevents the nuclear translocation of the ISGF3 transcription factor complex and reduces the induction of interferon-stimulated genes.