Comparison of the amino acid sequences of nine different serotypes of hepatitis B surface antigen and genomic classification of the corresponding hepatitis B virus strains

Abstract

The surface (S) genes of 12 hepatitis B viruses (HBVs) encoding nine different serotypes of hepatitis B surface antigen (HBsAg) were amplified by the polymerase chain reaction and sequenced. These represented the eight strains of HBV, PI to P8, defined at an international workshop on HBsAg subtypes in Paris in 1975, and the adrq-subtype. The S genes from additional HBV strains, one ayw4, one adw4 and one aywl, of sub-Saharan African origin, were also sequenced. The relationship of these 12 new S gene sequences to those of the 20 published previously was investigated by constructing a phylogenetic tree, which confirmed a previous classification into four groups, designated A to D, based on 18 complete HBV genomes. When relating our sequenced S genes to these genomic groups, aywl of African origin and P6 (adw2) were both allocated to group A, the reference P1 (aywl of Vietnamese origin) was allocated to group B, P5 (ayr), P8 (adr) and adrq-were all related to group C, and P2 (ayw2) and P3 (ayw3) could both be allocated to group D. Interestingly, the S genes of w4 serotype viruses, i.e. P4 (ayw4) and P7 (adw4q-), differed by 4% or more from both previous groups and from each other, suggesting their classification into two new groups, for which the designations E and F are proposed. Genomes specifying ayw were also found in groups A and B; previously sequenced genomes specifying the ayw subtype have all been confined to group D. There were indications that the epitope for subdeterminants of w resided at amino acid positions 125 to 127. Thus, at positions 125 and 127, aywl, ayw2 and adw2 had T and P residues, respectively, whereas M and T residues were at the corresponding positions ofayw3. Both ayw4 and adw4 had L at residue 127, and all strains expressing r, apart from P5, had an I instead of a T residue at position 126.

A unique segment of the hepatitis B virus group A genotype identified in isolates from South Africa.

“…A Lys to Arg switch at amino acids 122 and 160 of the S gene defines the d\y and w\r serotype specificities, respectively (Okamoto et al, 1987(Okamoto et al, , 1989. Ile"#' is thought to abolish the w determinant and thus define the r determinant (Norder et al, 1992). No other sites previously regarded as d\y or w\r determinants have consistently maintained their specificity as global sequence data accumulate.…”

“…Also grouping with these unique South African specimens was the Zimbabwean isolate (A45), the French isolate (A04) and clone pFDW294 (A42) from the Philippines, previously observed to be most similar to the Zimbabwean isolate. When the preS2 sequences from Kidd-Lju$ nggren et al (1994) and the S only sequences from Norder et al (1992) are included in the analyses the new subgroup expands to 23 (including 66n7 % of the southern African specimens) ; 19 of these (82n6 %) are African in origin since the Mozambican PLC\PRF\5 hepatoma cell line sequence as well as a sequence from Cameroon and the three incomplete South African sequences cluster with this group. Of interest, the only other addition to the group is KiddLju$ nggren's specimen LS (A10) from the Philippines.…”

Analysis of the entire nucleotide sequence of hepatitis B virus genotype B in the Philippines reveals a new subgenotype of genotype B

“…Eight different genotypes of HBV, named A-H, have been determined to date (Okamoto et al, 1988;Norder et al, 1992;Stuyver et al, 2000;Arauz-Ruiz et al, 2002). The distribution of genotypes throughout the world has been confirmed, with genotype A being predominant in North…”

Determinants for sustained HBeAg response to lamivudine therapy

“…12,13 There are remarkable differences in the clinical and virologic characteristics between patients with different genotypes. 14 It has been suggested that genotype C is associated with more severe liver disease and genotype B is associated with the development of hepatocellular carcinoma in young noncirrhotic patients in Taiwan.…”