The major envelope protein of hepatitis B surface antigen (HBsAg) which consists of 226 amino acids is coded by the S gene. The common antigenic determinant epitopes of all subtypes of HBsAg are found in á´determinant which is between amino acids 124 to 147. This important region is considered to be within a larger antigenic area called the major hydrophilic region (NHR), and targeted antibodies against these epitopes are used in standard assays for HBsAg to diagnose hepatitis B virus (HBV) infection. However, HBsAg negative chronic hepatitis B (CHB) cases with a detectable level of HBV DNA by Polymerase chain reaction (PCR) are emerging. This is defined as occult HBV infection and has been reported in 9.4% of CHB patients. Various relevant mutations have been implicated in such HBsAg negativity.
2)Source:
Human Plasma/Serum
3)Markers:
HBsAg (-), Anti-HBs 3 mIU/ml), HBeAg(+), Anti-HBe(+), HBV DNA (29.3 pg/ml), ALT (130IU/L)
4)Genotype:
Genotype C and subtype adr
5)Features:
Pre-S2 deletion mutant: The pre-S2 amplification products showed deletion from nucleotide 23 to 55. This finding was consistent with the deletion of amino acids 12 to 22 in the pre-S2 regions
Mutations on the á´determinant: PCR amplification and sequencing analyses revealed point mutations resulting in amino acid substitutions at the group á´determinant.
YMDD Mutation: A mutation in the YMDD (tyrosine, aspartate, aspartate) motif of the viral polymerise (reverse transcriptase) was noticed as methionine 204 to isoleucine (rtM204I)
Figure 1: Amino acid substitution within the á´ loop structure of HBsAg protein. Sequencing revealed substitutions at position I126S, T1311N, M133T and S136Y in the á´ determinant of the S gene. Black circles represent residues with mutations while gray circles represent cysteines. White circles represent other residues.