A new algorithm for deduction of hepatitis B surface antigen subtype determinants from the amino acid sequence

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Hepatitis B virus (HBV) subtypes are challenging to associate with genotypes due to geographical variations.
• Understanding the molecular basis of HBsAg subtype reactivity is crucial for serologic diagnostics.

Purpose of the Study:

• To re-examine HBV subtypes and identify specific HBsAg amino acids responsible for serologic reactivity.
• To resolve problematic genotype/subtype associations in geographically diverse serum specimens.

Main Methods:

• Phylogenetic analysis of DNA sequences from 491 HBsAg-positive specimens to determine genotypes.
• Application of an algorithm based on HBsAg amino acid sequence for subtyping.
• Serological subtyping of problematic samples to validate sequence-based findings.

Main Results:

• Three isolates exhibited unusual genotype/subtype associations.
• Amino acid positions 122, 127, 140, 159, and 160 were identified as critical for HBsAg subtype reactivity.
• Amino acid position 134 was found to be non-essential for subtype reactivity, contrary to previous assumptions.

Conclusions:

• HBsAg amino acid positions 122, 127, 140, 159, and 160 are definitively involved in HBsAg reactivity.
• Reactivity for subtypes d, y, and r is governed by single amino acid changes.
• Reactivity for subtype w is determined by a combination of amino acid changes at positions 122, 127, 140, and 159.