The C gene of hepatitis B virus (HBV) codes for a nucleocapsid protein made of 183 amino acid residues and is preceded in phase by the precore (pre-C) region, encoding 29 residues. The pre-C-region product is required for the synthesis and secretion of hepatitis B e antigen (HBeAg), which is made of the C-terminal 10 amino acid residues of the pre-C-region product and the N-terminal 149 residues of the C-gene product. HBV mutants with pre-C-region defects prevailed in the circulation of three asymptomatic carriers as they seroconverted from HBeAg to the corresponding antibody (anti-HBe), and these mutants finally replaced nondefective HBV. HBV DNA clones were propagated from sera of an additional 15 carriers with anti-HBe and sequenced for the pre-C region. Essentially all HBV DNA clones (56 of 57 [98%]) revealed mutations that prohibited the translation of a functional pre-C-region product. A point mutation from G to A at nucleotide 83, converting Trp-28 (TGG) to a stop codon (TAG), was by far the commonest and was observed in HBV DNA clones from 16 (89%) of 18 carriers seropositive for anti-HBe. In addition, there were point mutations involving ATG codon to abort the translation initiation of the pre-C region, as well as deletion and insertion to induce frameshifts. Such mutations leading to pre-C-region defects were rarely observed in persistently infected individuals positive for HBeAg or in patients with type B acute hepatitis after they had seroconverted to anti-HBe. These results would indicate a selection of pre-C-defective mutants in persistently infected hosts, along with seroconversion to anti-HBe, by immune elimination of hepatocytes harboring nondefective HBV with the expression of HBeAg.

Hepatitis B viruses with precore region defects prevail in persistently infected hosts along with seroconversion to the antibody against e antigen.

Hepatitis B virus genotypes.

A 681 nucleotide fragment of the hepatitis B virus (HBV) genome was sequenced that corresponded to the complete gene for hepatitis B surface antigen (HBsAg) in 80 HBsAg- and hepatitis B e antigen (HBeAg)-positive sera of diverse geographical origins. These and 42 previously published HBV sequences within the S gene were used for the construction of a dendrogram. In this comparison, each of the 122 HBsAg genes was found to be related to one or other of the six previously identified genomic groups of HBV, A to F. The HBV strains within each genomic group showed a characteristic geographical distribution. Group A genomes were represented by 23 strains mainly originating in northern Europe and sub-Saharan Africa. The group B and C genomes, represented by 17 and 28 strains respectively, were confined to populations with origins in eastern Asia and the Far East. The group D genomes, represented by 38 strains, were found worldwide, but were the predominant strains in the Mediterranean area, the Near and Middle East, and in south Asia. Group E genomes, represented by nine strains, were indigenous to western sub-Saharan Africa as far south as Angola. There were indications that the F group, made up of six strains, represented the genomic group of HBV among populations with origins in the New World. Thus, HBV has diverged into genomic groups according to the distribution of mankind in the different continents. As well as giving information on the genetic relationship of HBV strains of different geographical origin, this study also provides information on the primary structure of HBsAg in different regions of the world. Such data might prove valuable in explaining the reported failures to obtain protection with current HBV vaccines.

Genetic relatedness of hepatitis B viral strains of diverse geographical origin and natural variations in the primary structure of the surface antigen

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.510290336

High prevalence of 1762T 1764A mutations in the basic core promoter of hepatitis B virus isolated from black africans with hepatocellular carcinoma compared with asymptomatic carriers

The preS2/S genes of hepatitis B virus isolated from 29 acutely or chronically infected individuals in the Gauteng province of South Africa were sequenced. Phylogenetic analysis of these sequences in comparison with global isolates from the GenBank database showed that 24 sequences clustered with genotypic group A, three with genotypic group D and one each with genotypic groups B and C. Group A isolates had greater identity with groups D (variation of 6.6%) and E (6.8%) than with the Eastern groups B (7.4%) and C (8.1%) and were most different from group F (11.0%). Of the South African group A specimens, 59.1% clustered with two global sequences to form a discrete segment which we have called subgroup A. The amino acid differences that set these isolates apart from the rest of group A tended to cluster in the preS2 region (amino acids 7, 10, 32, 35, 47, 48, 53 and 54), with a few changes occurring in the major surface antigen (amino acid sites 207 and 209). Analysis of isolates showed that there was a 9-fold higher prevalence of the ay determinant in South Africa than previously reported.

A unique segment of the hepatitis b virus group a genotype identified in isolates from south africa

The complete nucleotide sequence was determined for a hepatitis B virus genome of subtype adw (pFDW294) isolated and cloned from the plasma sample of a Philippino. The genome was 3221 base-pair long with a point mutation at the 1376th nucleotide that affected the coding capacity of the P and X genes. There was a wide range of sequence divergence among pFDW294 and the reported three genomes of the same subtype (1.1–9.9%), occurring more often in the pre-S region and the S gene than in the pre-C region and the C gene.

Nucleotide sequence of a hepatitis B virus genome of subtype adw isolated from a Philippine: Comparison with the reported three genomes of the same subtype

Ankylosing spondylitis has been shown to be highly associated with HLA-B27 in Caucasian patients. This is also present in other ethnic groups. This study was conducted to determine the frequency distribution of HLA antigens in Filipinos and determine the association of ankylosing spondylitis. 
Twenty patients satisfying the criteria for ankylosing spondylitis and 192 unrelated controls were HLA-A and B typed. Blood from these subjects were typed using NIH lymphocyte microcyto-toxicity method. 
Of the unrelated controls, the frequencies of HLA A9 (w24), B40, A1, B5, Bw22 were increased and B13, B18, Bw35 were decreased. B27 had a frequency of 5.2%. A very significant high frequency of B27 (90%) was found in patients with ankylosing spondylitis with a very high relative risk of 163. A11 had a frequency of 55% with a relative risk of 3.37 which was not significant while B18 had an 18% frequency and a relative risk of 10.5 which was significant. 
This study reaffirms the high degree of association of ankylosing spondylitis with HLA B27 and suggests than B18 may be an additional genetic marker for this disease.

Carlita C. Chavez

Papers

Nucleotide sequence of a hepatitis B virus genome of subtype adw isolated from a Philippine: Comparison with the reported three genomes of the same subtype

HLA Antigens in Filipinos with Ankylosing Spondylitis*