Isolation of a hepadnavirus from the woolly monkey, a New World primate

Abstract

Hepatitis B virus (HBV) infections are a major worldwide health problem with chronic infections leading to cirrhosis and liver cancer. Viruses related to human HBV have been isolated from birds and rodents, but despite efforts to find hepadnaviruses that infect species intermediate in evolution between rodents and humans, none have been described. We recently isolated a hepadnavirus from a woolly monkey (Lagothrix lagotricha) that was suffering from fulminant hepatitis. Phylogenetic analysis of the nucleotide sequences of the core and surface genes indicated that the virus was distinct from the human HBV family, and because it is basal (ancestral) to the human monophyletic group, it probably represents a progenitor of the human viruses. This virus was designated woolly monkey hepatitis B virus (WMHBV). Analysis of woolly monkey colonies at five zoos indicated that WMHBV infections occurred in most of the animals at the Louisville zoo but not at four other zoos in the United States.The host range of WMHBV was examined by inoculation of one chimpanzee and two black-handed spider monkeys (Ateles geoffroyi), the closest nonendangered relative of the woolly monkey. The data suggest that spider monkeys are susceptible to infection with WMHBV and that minimal replication was observed in a chimpanzee. Thus, we have isolated a hepadnavirus with a host intermediate between humans and rodents and establishes a new animal model for evaluation of antiviral therapies for treating HBV chronic infections.

Analysis of Host Range Phenotypes of Primate Hepadnaviruses by In Vitro Infections of Hepatitis D Virus Pseudotypes

“…1A). This host range difference was anticipated, since WMHBV does not efficiently infect chimpanzees in vivo (18). In spider monkey hepatocytes, WM-HDV particles showed a greater infectivity in the presence of PEG than they did in chimpanzee cells, and some infection was observed in the absence of PEG (Fig.…”

“…Hepadnaviruses, like HBV, characteristically display very narrow host ranges that extend only to closely related species. The discovery and characterization of a nonhuman primate hepadnavirus from woolly monkeys confirmed the restrictions on the transmissibility of the virus between species, as chimpanzees were not susceptible to an efficient infection with woolly monkey hepatitis B virus (WMHBV) (18). However, analyses of the host range of WMHBV indicated that the host range extends to the close relative of the woolly monkey, the black-handed spider monkey; both primates are within the Atelidae family and the Atelinae subfamily.…”

Structure of pre-S2 N- and O-linked glycans in surface proteins from different genotypes of hepatitis B virus

“…Since Thr-37, embedded in a sequence context favourable for O-glycosylation, is highly conserved in the pre-S2 domains of HBV genotypes B-F, in all primate hepatitis B virus genomes (Bartholomeusz & Schaefer, 2004) including the virus from the New World woolly monkey (Lanford et al, 1998) and even in the otherwise highly divergent pre-S2 sequence of WHV, respective threonine residues might be similarly glycosylated. The O-glycosylation at Thr-37 of pre-S2, however, cannot be essential for HBV genotype A, which exhibits no Thr within the range from aa 32 to 55, but contains numerous Ser residues in this region, which, as shown in this study, are not O-glycosylated.…”

Nomenclature for antiviral-resistant human hepatitis B virus mutations in the polymerase region

“…1). In the woolly monkey hepatitis virus 63 and rodent hepatitis virus rt domain, there is length variability between conserved regions A and B, resulting in 346 and 342 amino acids for the respective rt domains (data not shown).…”