The transmission of hepadnaviruses between their natural hosts, humans, non-human primates, and birds, including intra-species host transmission and cross-species transmission, is a topic of study in virology. Hepadnaviruses are a family of viruses that can cause liver infections in humans and animals. They are Group VII viruses that possess double-stranded DNA genomes and replicate using reverse transcriptase. This unique replication strategy, combined with their extremely small genomes and a very narrow host and tissue tropism, has distinguished them enough to be classified in the family Hepadnaviridae. There are two recognized genera:
Orthohepadnavirus, type species: hepatitis B virus (HBV) Avihepadnavirus, type species: duck hepatitis B virus (DHBV)
Structure
With the example of human HBV: the particular feature of the HBV structure is the presence of three different forms in the plasma of infected patients:
Dane particle (diameter ≈ 42 nm): the complete virion, which is infectious and consists of an enveloped icosahedral nucleocapsid containing the viral genome, consisting of core protein and protecting the partially double-stranded DNA genome, bounding with DNA polymerase. The capsid is enveloped by a lipid bilayer that contains three forms of envelope proteins: small (S) proteins, intermediated (M) proteins, and large (L) proteins, and these proteins have different surface antigenes domains which contribute the viral infectivity: L protein (Pre S1, Pre S2, S), M protein (Pre S2, S), S protein (S). In figure 1, showing the simplified structure of HBV particles. Subviral sphere particles (diameter ≈ 22 nm), these smaller, non-infectious and are the most abundant particle in the blood of an infected one. They are assumed to have the ability of absorbing virus-neutralizing antibodies to facilitate the virus spread and maintenance in the host. Filaments (diameter ≈ 22 nm, length: 50 nm-70 nm), which are less known about, but they are actually consisted of many subviral sphere particles.
Genome
As with the example of HBV, showing in figure 2, four open reading frames are encoded (ORFs), all ORFs are in the same direction, defining the minus- and plus-strands. And the virus has four known genes, which encode the core protein, the virus polymerase, surface antigens (preS1, preS2, and S) and the X protein. The minus-strand DNA is complete and spans the entire genome, while the plus strand spans only about two-thirds of the genome length and have variable 3' ends. But for the avihepadnaviruses they normally extend plus-strands almost all the way to the modified 5' end. The minus-strand is linked to the viral reverse transcriptase and can encode all the known viral proteins, but the plus-strain cannot encode viral proteins.
Replication
With the example of HBV: the mechanisms of infecting hepatocytes are still not well understood, but among the studies, it was revealed that the PreS1 domain of the L protein, plays a critical role in the infection, thus exhibiting different host specificity between different hepadnaviruses. Figure show the general process of the HBV infecting host cell: attachment-entry-uncoating-replicate-assembly-release. About the viral entry, several proteins have been identified as possible virus receptors, and studies show that the binding of virion with receptors can be neutralized by anti-PreS1 antibodies. The replication is the unique reverse transcriptase strategy: after uncoating, nucleocapsids are transported to the host cell nucleus, the virion DNA will be converted into covalently closed circular (CCC) DNA, the template for the transcription of the viral RNAs. Then undergoes transcription by the host cell RNA polymerase and the transcript is translated by host cell ribosomes; the high capacity of this replicating part contributes many errors which may help the virus adapt to the host. New virus particles are formed, which acquire lipid from the endoplasmic reticulum of the host cell, and the genome is packaged within these particles, which then bud off from the cell; and some part of the new genome may return to the host cell nucleus for replication more genomes.
Phylogenetic tree All the members of family hepadnaviridae share remarkable similarities in the genome organization and the replication strategies, however, it also shows the differences between different species, different genotypes, and different subtypes. The species specificity of them are determined, to some extent, at the level of virus entry, involving the PreS1 part of the large envelop protein L, which could be a reason for their specificity of host range.
Orthohepadnavirus Viruses in this genus infect mammals, including human, apes, and rodents, with a narrow host range for each virus. The only known natural host for HBV is human, chimpanzees maybe infected experimentally. The orthohepadnaviruses have been divided into four distinct species, with HBV (human hepatitis B virus), WHV (woodchuck hepatitis virus), GSHV (ground squirrel hepatitis virus ), and WMHBV (woolly monkey hepatitis B virus) as the prototypes, based on the host range from a limited number of studies. From the result of molecular studies about the polymerase chain reaction (PCR)-based assays, information about the number and geographic distribution of HBV genotypes and naturally occurring HBV mutants are gained. Eight HBV genotypes, A to H, have been identified in human and three closely related genotypes in apes are found, like gibbon, orangutan, chimpanzee; and he eight HBV genotypes have further diverged into at least 24 subgenotypes. With different analysis, including analysis of recombinants, the new Genotype J was provisionally assigned to be a genetic variant of HBV which is divergent from known human and ape genotypes, it was isolated from a Japanese patient.
Avihepadnavirus Viruses in this genus exclusively infect birds; duck hepatitis B virus (DHBV) and heron hepatitis B virus (HHBV) are the prototypes. Avihepadnaviruses have been detected in various duck species. As the same with the orthohepadnaviruses, avihepadnaviruses have a rather narrow host range, but its common host are ducks and geese, other possible hosts are herons, stocks and crane.
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