Ded and partly single-stranded. DNA is released into the nucleus where gaps in the DNA are filled-in by the host machinery. From the resulting covalently closed circular DNA, full size pregenomic RNA, is transcribed in the nucleus by the host enzymes. The pregenomic RNA is transported to the cytoplasm and assembles into nascent viral capsids together with the virally encoded reverse transcriptase and a cellular protein kinase, tentatively identified as serine arginine protein kinase 1 and 2.103 The RNA containing assembled particles are immature virions. Maturation occurs when the packaged RNA is reversed transcribed inside the immature capsid into genomic DNA. Studies on duck hepatitis B showed that viral maturation is associated with phosphorylation and dephosphorylation104 at a number of sites located at the C-terminus of the core proteins.105 The phosphorylation state was found to affect the conformational state of the C-terminus of the core protein.106 Furthermore, S245 phosphorylation was suggested to play a central role in nuclear targeting and DNA release from capsids during viral infection.107 Recent in vitro studies on HBV demonstrated binding of SRPK to the C-terminus, leading the authors to propose that the kinase functions as a non-canonical chaperone, preventing premature self-assembly and packaging of nonspecific RNA.108 The cytoplasm of an HBV-infected cell contains both immature and mature particles. The mature, DNA-containing capsids may be enveloped, released from the cell and spread to initiate infection of other cells,109 or they may re-enter the nucleus for additional rounds of transcription and viral propagation. The virus enters cells via receptor mediated endocytosis and is taken up by the endosome. Following processing in the endosomal compartment the genome-containing nucleocapsid is released into the cytoplasm.110 The capsid then travels in a microtubule dependent motion toward the nucleus.111 Nuclear entry of Hepadnaviruses is via the nuclear pore. In human HBV, an NLS sequence of the capsid protein is located at the arginine-rich C-terminal domain, which, in the mature virus, is facing the interior of the capsid.112 In contrast, duck HBV does not contain an arginine-rich CTD. SB-203580 supplier R-roscovitine Nevertheless, an NLS was identified in the core protein of DHBV.113 Experiments with HBV core proteins synthesized in E. coli have suggested that phosphorylation of the internal domain of the capsid protein leads to exposure of the NLS114 by extrusion of the C-terminus through a flexible linker hinge.115 However, it is equally possible that the CTD transiently extrudes from holes in the capsid, allowing exposure of nuclear localization signals, phosphorylation sites, and dephosphorylation sites.108 It has been demonstrated that HBV capsomers bound RNA at high affinity, forming T = 4 capsids, whereas binding to DNA was poor, resulting in a mixture of non-capsid complexes.116 The authors proposed that capsids that assemble on RNA are stabilized by the negatively charged, flexible nucleic acid scaffold. However as they mature by reverse transcription they reach a 
metastable state, due to the double stranded DNA coiled 
spring.116 As opposed PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19856273 to the flexibility RNA, double-stranded DNA is a relatively stiff polymer that does not readily bend or circularize. The metastable state of mature particles, in which the mechanical force exerted by the DNA is comparable to the capsid protein-protein interactions, may contribute to extrusion of the C-t.Ded and partly single-stranded. DNA is released into the nucleus where gaps in the DNA are filled-in by the host machinery. From the resulting covalently closed circular DNA, full size pregenomic RNA, is transcribed in the nucleus by the host enzymes. The pregenomic RNA is transported to the cytoplasm and assembles into nascent viral capsids together with the virally encoded reverse transcriptase and a cellular protein kinase, tentatively identified as serine arginine protein kinase 1 and 2.103 The RNA containing assembled particles are immature virions. Maturation occurs when the packaged RNA is reversed transcribed inside the immature capsid into genomic DNA. Studies on duck hepatitis B showed that viral maturation is associated with phosphorylation and dephosphorylation104 at a number of sites located at the C-terminus of the core proteins.105 The phosphorylation state was found to affect the conformational state of the C-terminus of the core protein.106 Furthermore, S245 phosphorylation was suggested to play a central role in nuclear targeting and DNA release from capsids during viral infection.107 Recent in vitro studies on HBV demonstrated binding of SRPK to the C-terminus, leading the authors to propose that the kinase functions as a non-canonical chaperone, preventing premature self-assembly and packaging of nonspecific RNA.108 The cytoplasm of an HBV-infected cell contains both immature and mature particles. The mature, DNA-containing capsids may be enveloped, released from the cell and spread to initiate infection of other cells,109 or they may re-enter the nucleus for additional rounds of transcription and viral propagation. The virus enters cells via receptor mediated endocytosis and is taken up by the endosome. Following processing in the endosomal compartment the genome-containing nucleocapsid is released into the cytoplasm.110 The capsid then travels in a microtubule dependent motion toward the nucleus.111 Nuclear entry of Hepadnaviruses is via the nuclear pore. In human HBV, an NLS sequence of the capsid protein is located at the arginine-rich C-terminal domain, which, in the mature virus, is facing the interior of the capsid.112 In contrast, duck HBV does not contain an arginine-rich CTD. Nevertheless, an NLS was identified in the core protein of DHBV.113 Experiments with HBV core proteins synthesized in E. coli have suggested that phosphorylation of the internal domain of the capsid protein leads to exposure of the NLS114 by extrusion of the C-terminus through a flexible linker hinge.115 However, it is equally possible that the CTD transiently extrudes from holes in the capsid, allowing exposure of nuclear localization signals, phosphorylation sites, and dephosphorylation sites.108 It has been demonstrated that HBV capsomers bound RNA at high affinity, forming T = 4 capsids, whereas binding to DNA was poor, resulting in a mixture of non-capsid complexes.116 The authors proposed that capsids that assemble on RNA are stabilized by the negatively charged, flexible nucleic acid scaffold. However as they mature by reverse transcription they reach a metastable state, due to the double stranded DNA coiled spring.116 As opposed PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19856273 to the flexibility RNA, double-stranded DNA is a relatively stiff polymer that does not readily bend or circularize. The metastable state of mature particles, in which the mechanical force exerted by the DNA is comparable to the capsid protein-protein interactions, may contribute to extrusion of the C-t.
