Hepatitis B virus genotypes, core gene variability and ethnicity in the Pacific region.

BACKGROUND/AIMS: The world-wide distribution of hepatitis B virus (HBV) genotypes follows a geographic pattern under the influence of ethnic background. METHODS: Forty eight core genes from four pacific islands were compared with the following findings. RESULTS: First, island-specific variant substitutions were found for only two out of four islands. Second, 11 amino acid and 90 nucleotide changes specific for pacific genotypes C and D were defined. Third, the nucleotide diversity of genotype C (all but one were silent) was greater than that of genotype D. CONCLUSIONS: These results suggest an early appearance of genotype C in the pacific with few subsequent amino acid changes because of shared immunological responses across the region followed by random silent changes, some of which reflect isolation of individual island populations. Genotype D appeared later.

Intracellular distribution of hepatitis B virus core protein expressed in vitro depends on the sequence of the isolate and the serologic pattern.

Intracellular localization of hepatitis B core antigen (HBcAg) in vivo varies with liver cell damage. Localization of HBcAg was studied using transfection of cloned HBcAg variants. Twenty-six samples were obtained from 14 patients with liver disease; 10 were hepatitis B e antigen positive, and 16 were anti-hepatitis B e (HBe) positive. In hepatitis B e antigen (HBeAg)-positive patients, HBcAg predominantly localized in the nucleus; in anti-HBe-positive patients, it accumulated mainly in the cytoplasm. Of the 13 samples with nuclear localization, 9 were HBeAg positive; 5 of 13 had C-terminus and/or B cell epitope mutations. All but 1 of the 13 samples with predominantly cytoplasmic localization were anti-HBe positive; all 13 had mutations. Reversion of mutant sequences with cytoplasmic expression back to the wild type led to a shifting back to nuclear distribution. Thus, the pattern of HBcAg localization in vitro depends on sequence and the serologic pattern of chronic infection, paralleling the situation in vivo.