Amino Acid Polymorphism in Hepatitis B Virus Associated With Functional Cure

Area of Science:

• Virology
• Hepatology
• Molecular Biology

Background:

• Identifying prognostic markers for chronic hepatitis B (CHB) is crucial for effective treatment strategies.
• The isoleucine to leucine substitution at amino acid 97 (I97L) in the hepatitis B core region was previously identified as a key predictor in stable hepatitis.
• Understanding the impact of I97L on the hepatitis B virus (HBV) life cycle is essential for elucidating hepatitis stabilization mechanisms.

Purpose of the Study:

• To investigate the clinical features and viral characteristics associated with the I97L substitution in HBV.
• To elucidate the mechanisms by which I97L affects the HBV life cycle and hepatitis stabilization.

Main Methods:

• A cohort of hepatitis B e antigen-negative CHB patients infected with wild-type (wt) or I97L HBV was analyzed.
• In vitro HBV production and infection systems using reporter viruses and cell culture-generated HBV were employed to evaluate the effects of I97L.

Main Results:

• Patients with HBV-I97L showed higher reductions in hepatitis B surface antigen and HBV DNA compared to HBV-I97wt.
• HBV-I97L exhibited significantly lower infectivity than HBV-I97wt.
• HBV-I97L virions primarily contained single-stranded HBV genomes, leading to reduced cccDNA synthesis efficiency.

Conclusions:

• The I97L substitution reduces cccDNA levels by producing immature, single-stranded genome virions.
• The diminished cccDNA synthesis associated with I97L may contribute to hepatitis stabilization in CHB patients.