Full-genome sequence analyses of hepatitis B virus (HBV) strains recoveredfrom chimpanzees infected in the wild: Implications for an origin of HBV

Hepatitis B virus (HBV) belongs to the genus Orthohepadnavirus of the famil y Hepadnaviridae. Having been found in various animals (duck, heron, woodch uck, ground squirrel, and primates), hepadnaviruses must have undergone a l ong history of evolution and may comprise more members than currently recog nized. Chimpanzees may also have their own hepadnavirus, even if it might b e very close to HBV. We analyzed HBV-like sequences from three chimpanzees (Pan troglodytes) that were most likely infected during their life in Afric a in the wild. Two chimpanzees (Ch256 and Ch258) possessed a viral genome o f 3182 nt in length with a 33-nt deletion in the preS1 region; which could not be classified into any of the six genotypes (A-F) of human HBV but was very homologous to a previously reported isolate from a London Zoo chimpanz ee. Phylogenetically distinct from the HBV-like sequences from gibbons, ora ngutans, and a gorilla so far reported, the Ch256 and Ch258 isolates would represent an indigenous chimpanzee HBV (tentatively ChHBV). A third chimpan zee (Ch195) had a 3212-nt genome, classifiable into the genotype E of HBV. Because HBV-E has been found mostly in Africans, Ch195 may have been Infect ed from a human source in Africa. However, an inverse scenario is also poss ible: a spread of HBV-E might have occurred from chimpanzees to humans a lo ng time ago in Africa. Analysis of the arginine-rich C-terminal region of t he core protein, which is well conserved among mammalian hepadnaviruses, in dicated that HBV-E/F and nonhuman primate hepadnaviruses are much closer th an HBV-A/B/C/D to the hepadnaviruses of woodchuck and ground squirrel. Our results support an "ex-nonhuman primate" hypothesis for the origin of HBV. (C) 2000 Academic Press.