W one 34 residue domain can orchestrate the myriad template switches and genome rearrangements that occur during reverse transcription. The assembly domain also contributes to reverse transcription; the capsid is not an inert container. Mutations to the Cp assembly domain, which affect assembly, support minus strand DNA synthesis but specifically abrogate all evidence of second strand synthesis. Similarly, the capsid is responsive to nucleic acid contents. rcDNA-filled cores are less stable than ssDNA-filled and ssRNA-filled cores based on sensitivity to nucleases and proteases as well as biophysical properties such as migration through a gel. Slight structural differences have been observed in dsDNA-filled capsids compared to RNA-filled capsids. The process of reverse transcription may itself destabilize the capsid. Based on calculations, the amount of stress AZ-6102 chemical information Author Neuromedin N web Manuscript Author Manuscript Author Manuscript Author Manuscript Antiviral Res. Author manuscript; available in PMC 2016 September 01. Zlotnick et al. Page 10 imposed on the HBV capsid by packaged dsDNA increases precipitously as the DNA approaches full-length. Author Manuscript Author Manuscript Author Manuscript Author Manuscript The Cp CTD and host partners Cp interacts with host proteins. A critical gap in the 
field is that only a few of these interactions have been described. The best understood feature is the CTD. CTD, normally located inside the core particle displays a nuclear localization signal on the exterior. The NLS is localized to the argininerepeats. As with many NLS sequences its activity is modulated by phosphorylation, but probably not in the usual way. A likely explanation is that phosphorylation weakens interaction of the CTDs with encapsidated nucleic acid. The CTDs bind importin / complexes or perhaps only importin, which act as adapters for transport of cores to the nuclear pores. In the nuclear pore itself, cores interact with the Nup153 and apparently dissociate during entry to the nucleus. NLS phosphorylation may be required for interaction with the nuclear pore complex. Of note, the destabilization of the core may occur before it reaches the nuclear pore as a function of core maturation presumably due to completion of rcDNA and change in CTD phosphorylation state. Indeed, cleavage of DNA-bound P protein appears to begin while core is in the cytoplasm. The identities of the kinases, there are likely more than one that actually phosphorylate the CTD, are open to question. Exhaustive analysis of immuno-reactivity and inhibitors suggest that CDK2 is packaged in cores. However, PKC and others have also been implicated. SRPK1 and SRPK2, normally associated with phosphorylation of spliceosomal proteins but also involved with retrovirus RNA synthesis, immunoprecipitates with the CTDs, modulates viral replication, and binds Cp and cores with a nanomolar dissociation constant. Indeed, the Cp CTD closely resembles the SR proteins that are SRPKs intended substrates. We suggest that different kinases play different roles in the viral lifecycle and may do so redundantly. Cp-directed antivirals HBV appears to follow an 
ordered assembly pathway where interactions between subunits are well defined. Deviations of assembly path or intersubunit geometry can lead to defective or aberrant particles that are not infectious. Inactive particles also sequester subunits that would otherwise be used for productive assembly leveraging the activity of a small PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19850718,22102576 number of antivir.W one 34 residue domain can orchestrate the myriad template switches and genome rearrangements that occur during reverse transcription. The assembly domain also contributes to reverse transcription; the capsid is not an inert container. Mutations to the Cp assembly domain, which affect assembly, support minus strand DNA synthesis but specifically abrogate all evidence of second strand synthesis. Similarly, the capsid is responsive to nucleic acid contents. rcDNA-filled cores are less stable than ssDNA-filled and ssRNA-filled cores based on sensitivity to nucleases and proteases as well as biophysical properties such as migration through a gel. Slight structural differences have been observed in dsDNA-filled capsids compared to RNA-filled capsids. The process of reverse transcription may itself destabilize the capsid. Based on calculations, the amount of stress Author Manuscript Author Manuscript Author Manuscript Author Manuscript Antiviral Res. Author manuscript; available in PMC 2016 September 01. Zlotnick et al. Page 10 imposed on the HBV capsid by packaged dsDNA increases precipitously as the DNA approaches full-length. Author Manuscript Author Manuscript Author Manuscript Author Manuscript The Cp CTD and host partners Cp interacts with host proteins. A critical gap in the field is that only a few of these interactions have been described. The best understood feature is the CTD. CTD, normally located inside the core particle displays a nuclear localization signal on the exterior. The NLS is localized to the argininerepeats. As with many NLS sequences its activity is modulated by phosphorylation, but probably not in the usual way. A likely explanation is that phosphorylation weakens interaction of the CTDs with encapsidated nucleic acid. The CTDs bind importin / complexes or perhaps only importin, which act as adapters for transport of cores to the nuclear pores. In the nuclear pore itself, cores interact with the Nup153 and apparently dissociate during entry to the nucleus. NLS phosphorylation may be required for interaction with the nuclear pore complex. Of note, the destabilization of the core may occur before it reaches the nuclear pore as a function of core maturation presumably due to completion of rcDNA and change in CTD phosphorylation state. Indeed, cleavage of DNA-bound P protein appears to begin while core is in the cytoplasm. The identities of the kinases, there are likely more than one that actually phosphorylate the CTD, are open to question. Exhaustive analysis of immuno-reactivity and inhibitors suggest that CDK2 is packaged in cores. However, PKC and others have also been implicated. SRPK1 and SRPK2, normally associated with phosphorylation of spliceosomal proteins but also involved with retrovirus RNA synthesis, immunoprecipitates with the CTDs, modulates viral replication, and binds Cp and cores with a nanomolar dissociation constant. Indeed, the Cp CTD closely resembles the SR proteins that are SRPKs intended substrates. We suggest that different kinases play different roles in the viral lifecycle and may do so redundantly. Cp-directed antivirals HBV appears to follow an ordered assembly pathway where interactions between subunits are well defined. Deviations of assembly path or intersubunit geometry can lead to defective or aberrant particles that are not infectious. Inactive particles also sequester subunits that would otherwise be used for productive assembly leveraging the activity of a small PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19850718,22102576 number of antivir.
