Hepatitis B core antigen can regulate NLRP3 inflammasome pathway in HepG2 cells

Area of Science:

• Immunology
• Virology
• Hepatology

Background:

• Hepatitis B virus (HBV) ORF C encodes Hepatitis B core antigen (HBcAg) and Hepatitis B e antigen (HBeAg).
• HBeAg is known to inhibit NLRP3 inflammasome activation and IL-1β production.
• The specific roles of HBcAg and combined ORF C proteins in inflammasome activation remain unclear.

Purpose of the Study:

• To investigate the impact of HBcAg and ORF C proteins on the NLRP3 inflammasome pathway.
• To elucidate the mechanisms underlying HBV-induced liver inflammation.

Main Methods:

• HepG2 cells were transfected with vectors expressing ORF C proteins and HBcAg.
• Cells were stimulated with lipopolysaccharide (LPS).
• NLRP3 inflammasome activation, IL-1β, and IL-18 levels were assessed using Western blot, qRT-PCR, ELISA, and immunofluorescence.

Main Results:

• LPS stimulation at 1000 ng/mL for 18-24 hours maximized NLRP3 and IL-1β expression in HepG2 cells.
• HBcAg significantly promoted LPS-induced NLRP3 inflammasome activation and IL-1β production.
• ORF C proteins, as a whole, did not show this promoting effect.

Conclusions:

• HBcAg, but not the combined ORF C proteins, enhances NLRP3 inflammasome activation and IL-1β production.
• This study uncovers a novel mechanism for HBV-associated liver inflammation.
• Findings may guide the development of new therapeutic strategies for HBV infection.