New Hepatitis B Virus of Cranes That Has an Unexpected Broad Host Range

Abstract

All hepadnaviruses known so far have a very limited host range, restricted to their natural hosts and a few closely related species. This is thought to be due mainly to sequence divergence in the large envelope protein and species-specific differences in host components essential for virus propagation. Here we report an infection of cranes with a novel hepadnavirus, designated CHBV, that has an unexpectedly broad host range and is only distantly evolutionarily related to avihepadnaviruses of related hosts. Direct DNA sequencing of amplified CHBV DNA as well a sequencing of cloned viral genomes revealed that CHBV is most closely related to, although distinct from, Ross' goose hepatitis B virus (RGHBV) and slightly less closely related to duck hepatitis B virus (DHBV). Phylogenetically, cranes are very distant from geese and ducks and are most closely related to herons and storks. Naturally occurring hepadnaviruses in the last two species are highly divergent in sequence from RGHBV and DHBV and do not infect ducks or do so only marginally. In contrast, CHBV from crane sera and recombinant CHBV produced from LMH cells infected primary duck hepatocytes almost as efficiently as DHBV did. This is the first report of a rather broad host range of an avihepadnavirus. Our data imply either usage of similar or identical entry pathways and receptors by DHBV and CHBV, unusual host and virus adaptation mechanisms, or divergent evolution of the host genomes and cellular components required for virus propagation.Infections caused by hepatitis B virus (HBV) remain one of the most serious medical challenges worldwide, with approximately 350 million humans being chronically infected. There is currently no established effective therapy available. HBVs are small enveloped DNA viruses constituting the family Hepadnaviridae and propagating their genome by reverse transcription of an RNA intermediate (22). As well as in humans, orthohepadnaviruses have been identified so far in rodents such as woodchucks (woodchuck hepatitis virus), ground and arctic squirrels (ground squirrel hepatitis virus and arctic squirrel hepatitis virus), and recently in Old World as well as New World primates including woolly monkeys, orangutans, gorillas, and gibbons (17, 18). Naturally occurring infections by avihepadnaviruses were first described in Pekin ducks (Anas domesticus) (duck hepatitis B virus DHBV) from China and the United States (13, 33) and were subsequently found in various other duck strains (references 21 and 29 and references therein). DHBV-related viruses have also been isolated from four other avian species, namely, grey heron (Ardea cinerea) (he- Extracellularly, virions contain partially double-stranded DNA of exquisitely compact size (3.0 to 3.3 kbp). Following arrival in the nucleus, the incoming viral genome is converted into covalently closed circular DNA and serves as the template for viral transcription. The genes of hepadnaviruses are all extensively overlapping and encode the envelope (pre-S and S), the nucleocapsid (core or C),...

Assembly and budding of a hepatitis B virus is mediated by a novel type of intracellular vesicles

“…The overall ultrastructure of the intracellular viral particles is similar, if not identical, to extracellular progeny as reported. 31 Furthermore, concurrence of both particle types in the same compartment is strongly suggestive for a common Immunogold particles were predominantly scattered in the cytosol (arrow heads) and at the limiting membrane of VCVs (black arrows), and rarely found inside the vesicles (white arrows). morphogenetic pathway.…”

Avian hepatitis B viruses: Molecular and cellular biology, phylogenesis, and host tropism

“…Despite its substantial sequence homology with DHBV, HHBV does not infect ducks and only very inefficiently primary duck hepatocytes [15] . Recently, we reported that cranes are naturally infected with a hepatitis B virus, designated CHBV [14] . Cranes are phylogenetically very distant from ducks and are more closely related to herons and storks ( Figure 1).…”

“…Since then, avihepadnaviruses have been detected in various duck species [10] including exotic ducks and geese [10] (DHBV), in snow geese [12] (SGHBV), a Ross' goose (RGHBV, GenBank Acc.No. M95589), white storks [13] (STHBV), demoiselle and grey crowned cranes [14] (CHBV) as well as grey herons [15] (HHBV). Like their mammalian counterparts, avihepadnaviruses have a rather narrow host range.…”

Mechanism of viral persistence and resistance to nucleoside and nucleotide analogs in chronic Hepatitis B virus infection

“…Our knowledge of the pathobiology of HBV infection has come from clinical studies and from experimental investigations performed in animal models. HBV belongs to the hepadnaviridae family that include animal viruses sharing the same replication strategy, ie woolly monkey hepatitis virus (WMHV) (Lanford et al, 1998), woodchuck hepatitis virus (WHV) (Summers et al, 1978), ground squirel hepatitis virus (GSHV) (Marion et al, 1980), artic squirel hepatitis virus (ASHV) (Testut et al, 1996), duck hepatitis B virus (DHBV) (Mason et al, 1980), heron hepatitis virus (HHV) (Sprengel et al, 1988), snow goose hepatitis virus (SGHV) (Sprengel et al, 1988), and crane hepatitis virus (Prassolov et al, 2003). Due to a narrow host range of the virus, the human HBV can only infect chimpanzee and several higher primates (Guidotti et al, 1999a;Lanford et al, 2000) as well as tupaia belengeri, a small primate which however does not support chronic infection (Walter et al, 1996).…”