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

Abstract

The human hepatitis B virus (HBV) and the duck hepatitis B virus (DHBV) share several fundamental features. Both viruses have a partially double-stranded DNA genome that is replicated via a RNA intermediate and the coding open reading frames (ORFs) overlap extensively. In addition, the genomic and structural organization, as well as replication and biological characteristics, are very similar in both viruses. Most of the key features of hepadnaviral infection were first discovered in the DHBV model system and subsequently confirmed for HBV. There are, however, several differences between human HBV and DHBV. This review will focus on the molecular and cellular biology, evolution, and host adaptation of the avian hepatitis B viruses with particular emphasis on DHBV as a model system.

Characterization of Nucleosome Positioning in Hepadnaviral Covalently Closed Circular DNA Minichromosomes

“…Given that hepatocytes are long-living cells, pressures on viral DNA segregation might be less or attenuated in the case of hepadnaviruses. For persistent hepadnaviral infection, stably maintaining cccDNA in the nucleus is crucial since the replenishment of viral RC DNA, the precursor of cccDNA, might be inef-ficient in the presence of viral large envelope protein, the negative regulator of RC DNA nuclear translocation (10,34). As the first step of understanding of hepadnaviral cccDNA maintenance in the nucleus, it is informative to clarify the overall structure of cccDNA minichromosomes, especially nucleosome positioning on cccDNA.…”

Start or End? ; One of the Biggest Mysteries is Finally Solved?

“…Hepadnaviruses are highly species specific and tissue specific and HBV never infects present hepatocyte-originated human hepatocellular carcinoma cell lines such as HepG2. [5,6], it is not easy to hatch and raise these kinds of animal and to prepare primary hepatocytes from these animals.As for in vitro infection systems, two systems are available at present; one is Primary Human Hepatocytes (PHH) or tree shrew (Tupaia belangen) [7] which is also susceptible to HBV as human and chimpanzee and another is HepaRG [8], a cultured Human Hepatocellular Carcinoma (HCC) cell line established from HCV caused HCC.These in vitro systems facilitate our knowledge about how HBV infects hepatocytes, but still not good enough because of their commercialism, invariability dependent on the lot and takes cost for preparation and time to induce infectivity.A recent splendid report by Yan et al may improve such inconvenience to study HBV [8]. For long time, we have been searching for HBV receptors and several molecules including those from the DHBV system were nominated as HBV receptors but they had never contributed establishment for HBV infection systems in vitro, though many data have suggested that the ligand on the HBV side for the receptor must be in the preS1 region [9][10][11].…”

“…Hepadnaviruses are highly species specific and tissue specific and HBV never infects present hepatocyte-originated human hepatocellular carcinoma cell lines such as HepG2. [5,6], it is not easy to hatch and raise these kinds of animal and to prepare primary hepatocytes from these animals.…”

Duck Hepatitis B Virus Requires Cholesterol for Endosomal Escape during Virus Entry

“…While some viruses achieve this directly at the plasma membrane, for the majority of viruses, fusion/penetration occurs in the cell interior (30). Evidence for endocytosis as the entry mode of hepatitis B viruses (HBVs) is growing (11,14,36). For duck HBV (DHBV) and primary duck hepatocytes (PDHs), it has been shown that virus binding is species and cell type specific, that the preS region of the large viral envelope protein governs viral entry, that a small number of virions bind and enter host cells, that viral uptake requires energy and proceeds with a remarkably slow kinetics, and that virus trafficking requires dynamic microtubules (11,14,36).…”

“…In addition, binding of human HBV to host cells is facilitated by proteoglycans (25,37). However, major issues such as the identity and distribution of cellular factors/receptors mediating virus entry and mode of entry are still unknown (11,14,36).…”