Human betaretrovirus protease (HBRV PR)

Human betaretrovirus (HBRV) protease is an essential enzyme produced by HBRV, a retrovirus closely related to the Mouse Mammary Tumor Virus (MMTV). This aspartic protease is responsible for the post-translational cleavage of the Gag and Gag-Pol polyprotein precursors into mature, functional proteins required for viral infectivity and structural integrity. HBRV has been implicated in the pathogenesis of Primary Biliary Cholangitis (PBC), where it is hypothesized to infect biliary epithelial cells and trigger a chronic inflammatory and autoimmune response. Due to the structural homology between HBRV protease and HIV-1 protease, several HIV protease inhibitors, most notably lopinavir and ritonavir, have been evaluated for their ability to suppress HBRV replication. Clinical research has focused on using these antiretroviral therapies to treat PBC patients who do not respond adequately to standard-of-care treatments like ursodeoxycholic acid. Targeting this protease offers a potential therapeutic pathway for managing PBC by addressing a possible underlying viral infection.

Other names

HBRV aspartic proteaseMouse mammary tumor virus-like virus proteaseMMTV-like proteaseBetaretrovirus protease

Protease inhibition; the drugs bind to the active site of the aspartic protease, preventing the cleavage of Gag and Gag-Pol polyproteins into functional viral proteins, thereby halting the production of infectious virions.