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