COMPLETE SEQUENCING OF A GIBBON HEPATITIS-B VIRUS GENOME REVEALS A UNIQUE GENOTYPE DISTANTLY RELATED TO THE CHIMPANZEE HEPATITIS-B VIRUS

We have sequenced the complete genome of a hepatitis B virus (HBV) str ain that was transmitted from a gibbon with chronic hepatitis B to a c himpanzee that subsequently developed acute hepatitis B. The genome wa s 3,182 nucleotides long and had a genetic organization identical to a nd including the characteristics of other mammalian hepadnaviruses. Th us, the regulatory elements, the direct repeats, and the four open rea ding frames (ORFs) of this virus were all maintained, although there w ere amino acid substitutions affecting all the ORFs. Within the S gene encoding for the hepatitis B surface antigen (HBsAg), the subtype cou ld be deduced as ayw3 in accordance with previous serological results. There were 25 amino acid substitutions affecting the P gene, 12 of wh ich were within the spacer region, This region, which was the most div ergent part of the genome compared to other HBV strains, also encodes for the pre-S proteins. A comparison with sequences of other hepadnavi ruses revealed that the genome of gibbon HBV was unique as compared to previously described HBV genotypes. It was most similar to the chimpa nzee HBV strain with which it shared 90.3% nucleic acid homology at th e level of the complete genome and 96.3% homology at the level of the S-gene region corresponding to HBsAg, although being a distinct genoty pe as compared to the latter virus. Analyses performed using five diff erent algorithms for phylogenetic tree construction showed more than 9 9% bootstrap support for the gibbon and the chimpanzee HBV to be group ed within the human HBV strains and that they represented later offsho ots than the HBV strains of genotype F. However, in most of the dendro grams both the gibbon and the chimpanzee strains represented early lin eages, indicating that these viruses are indigenous to their respectiv e hosts and not recent acquisitions from man. (C) 1996 Academic Press, Inc.