Hepatitis B virus X protein–Cyclophilin A protein–protein interaction (HBx–CypA PPI)

The Hepatitis B virus X protein (HBx)–Cyclophilin A (CypA) protein–protein interaction is a critical nexus in the life cycle of the Hepatitis B virus (HBV). HBx is a multifunctional non-structural protein (UniProt P03401) essential for viral replication, transactivation of host and viral genes, and the development of hepatocellular carcinoma (Tian et al., 2010, Journal of Virology). Cyclophilin A (PPIA, UniProt P62937), a host peptidyl-prolyl cis-trans isomerase, acts as a molecular chaperone that binds to HBx, facilitating its proper folding, stability, and functional activity (Qing et al., 2011). Research indicates that disrupting this interaction significantly impairs HBV replication and reduces the oncogenic potential of HBx. Therapeutic strategies targeting this interaction primarily involve cyclophilin inhibitors, such as Alisporivir (DEBIO-025), which are non-immunosuppressive derivatives of cyclosporine (Phillips et al., 2015, Journal of Hepatology). These drugs prevent CypA from binding to HBx, thereby suppressing viral load and potentially mitigating the progression of chronic hepatitis B to cirrhosis or cancer.

Other names

HBx-CypA interactionHBx-PPIA interactionHepatitis B virus X protein-Peptidyl-prolyl cis-trans isomerase A interaction

Inhibition of the host Cyclophilin A (PPIA) binding to the viral HBx protein, which prevents the chaperone-assisted folding and stabilization of HBx required for HBV replication (Tian et al., 2010).