DnaJ heat shock protein family (Hsp40) member B12 (DNAJB12) (DNAJB12)

DnaJ heat shock protein family (Hsp40) member B12 (DNAJB12) is a host chaperone protein located in the endoplasmic reticulum (ER) membrane that has been identified as the primary target for nucleic acid polymers (NAPs) in the treatment of chronic hepatitis B (HBV) and hepatitis D (HDV) infections (3.1.1, 3.2.2). It functions as a co-chaperone, assisting Hsp70 in the folding and assembly of transmembrane proteins and participating in endoplasmic reticulum-associated degradation (ERAD) (3.3.2). In HBV-infected cells, DNAJB12 is essential for the morphogenesis and secretion of subviral particles (SVPs), which are non-infectious particles produced in massive excess to decoy the host immune system (3.1.3, 3.2.1). NAPs like REP 2139 and REP 2165 bind to an exposed hydrophobic surface on the amphipathic alpha-helix of the DNAJB12 J-domain, preventing its interaction with Hsp70 and the proper folding of nascent Hepatitis B surface antigen (HBsAg) (3.2.3, 3.3.1). This leads to the intracellular degradation of HBsAg and a rapid decline in circulating HBsAg levels, which is thought to relieve immune exhaustion and facilitate a functional cure (2.2.1, 3.2.4).

Other names

Unidentified host protein with exposed hydrophobic surface involved in HBV subviral particle assembly/secretionHost protein target of NAPsNAP targetHsp40 chaperone DNAJB12DnaJ homolog subfamily B member 12ER-localized J-protein DNAJB12

Inhibition of subviral particle assembly and secretion by binding to an exposed hydrophobic surface (amphipathic alpha-helix) of the host chaperone DNAJB12, leading to the degradation of nascent HBsAg.