Hepatitis B virus Dane particles bind to human plasma apolipoprotein H

Area of Science:

• Virology
• Immunology
• Biochemistry

Background:

• Hepatitis B virus (HBV) infection remains a significant global health concern.
• Understanding host-pathogen interactions is crucial for developing therapeutic strategies.
• Apolipoprotein H (apo H) is a plasma protein with known immune-modulating functions.

Purpose of the Study:

• To investigate the specific binding interaction between human apolipoprotein H (apo H) and hepatitis B surface antigen (HBsAg).
• To identify the domains and molecular components of HBV involved in apo H binding.
• To correlate apo H-HBsAg binding with the stage of hepatitis B virus infection.

Main Methods:

• Utilized recombinant HBsAg proteins to map apo H binding sites.
• Investigated the role of phospholipids and metal ions (iron, zinc) in the binding interaction.
• Fractionated HBV particles using sucrose gradients and analyzed binding activity.
• Employed electron microscopy and PCR Southern blot to characterize viral particles.
• Assessed apo H-HBsAg binding in patient sera with known HBV markers.

Main Results:

• Apo H specifically binds to HBsAg, with a strong interaction observed with the myristylated pre-S1 domain.
• The binding is dependent on phospholipid components of the HBV envelope and is modulated by iron and zinc ions.
• Maximal apo H binding activity was associated with full Dane particles, identified in specific sucrose gradient fractions.
• Higher apo H binding activity was detected in sera from patients with active HBV replication.

Conclusions:

• Human apo H binds to the pre-S1 domain of HBsAg, involving phospholipids and influenced by metal ion oxidation states.
• Apo H binding is associated with infectious Dane particles and is elevated during active HBV replication.
• These findings suggest a potential role for apo H in the pathogenesis or immune response to HBV infection.