Core protein: A pleiotropic keystone in the HBV lifecycle

Antiviral Research

Volumn 121, Issue , 2015, Pages 82-93

  Zlotnick, Adam ^a   Venkatakrishnan, Balasubramanian ^a   Tan, Zhenning ^b   Lewellyn, Eric ^b   Turner, William ^b   Francis, Samson ^a,b  

^a INDIANA UNIVERSITY   (United States)

^b Assembly Biosciences Inc R D Main Facility   (United States)

Author keywords

Antiviral therapy; Capsid; Hepatitis B Virus; Self assembly

Indexed keywords

ANTIVIRUS AGENT; CAPSID PROTEIN; CIRCULAR DNA; CORE PROTEIN; HEPATITIS B CORE ANTIGEN; P22 CORE PROTEIN, HEPATITIS B VIRUS; PROTEIN BINDING;

HEPATITIS B VIRUS; HOST; HUMAN; LIFE CYCLE; NONHUMAN; PLEIOTROPY; PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN STRUCTURE; REVERSE TRANSCRIPTION; REVIEW; METABOLISM; MOLECULAR MODEL; PHYSIOLOGY; PROTEIN CONFORMATION; PROTEIN MULTIMERIZATION; VIRUS ASSEMBLY; VIRUS REPLICATION;

HEPATITIS B VIRUS; MIRIDAE;

HEPATITIS B CORE ANTIGENS; HEPATITIS B VIRUS; MODELS, MOLECULAR; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN MULTIMERIZATION; VIRAL CORE PROTEINS; VIRUS ASSEMBLY; VIRUS REPLICATION;

EID: 84936972283     PISSN: 01663542     EISSN: 18729096     Source Type: Journal    
DOI: 10.1016/j.antiviral.2015.06.020     Document Type: Review

References (176)

1. T.M. Abraham, and D.D. Loeb Base pairing between the 5' half of epsilon and a cis-acting sequence, phi, makes a contribution to the synthesis of minus-strand DNA for human hepatitis B virus J. Virol. 80 2006 4380 4387
2. T.M. Abraham, and D.D. Loeb The Topology of Hepatitis B Virus Pregenomic RNA Promotes Its Replication J. Virol. 81 2007 11577 11584
3. C.G. Alexander, M.C. Jurgens, D.A. Shepherd, S.M. Freund, A.E. Ashcroft, and N. Ferguson Thermodynamic origins of protein folding, allostery, and capsid formation in the human hepatitis B virus core protein Proc. Natl. Acad. Sci. U.S.A. 110 2013 E2782 E2791
4. R. Bartenschlager, M. Junker-Niepmann, and H. Schaller The P gene product of hepatitis B virus is required as a structural component for genomic RNA encapsidation J. Virol. 64 1990 5324 5332
5. R. Bartenschlager, and H. Schaller Hepadnaviral assembly is initiated by polymerase binding to the encapsidation signal in the viral RNA genome EMBO J. 11 1992 3413 3420
6. S.H. Basagoudanavar, D.H. Perlman, and J. Hu Regulation of hepadnavirus reverse transcription by dynamic nucleocapsid phosphorylation J. Virol. 81 2007 1641 1649
7. L. Belloni, L. Li, G.A. Palumbo, S.R. Chirapu, L. Calvo, M.G. Finn, U. Lopatin, A. Zlotnick, and M. Levrero HAPs hepatitis B virus (HBV) capsid inhibitors block core protein interaction with the viral minichromosome and host cell genes and affect cccDNA transcription and stability Hepatology 58 2013 277A
8. L. Belloni, T. Pollicino, F. De Nicola, F. Guerrieri, G. Raffa, M. Fanciulli, G. Raimondo, and M. Levrero Nuclear HBx binds the HBV minichromosome and modifies the epigenetic regulation of cccDNA function Proc. Natl. Acad. Sci. U.S.A. 106 2009 19975 19979
9. J.Z. Bereszczak, R.J. Rose, E. van Duijn, N.R. Watts, P.T. Wingfield, A.C. Steven, and A.J. Heck Epitope-distal effects accompany the binding of two distinct antibodies to hepatitis B virus capsids J. Am. Chem. Soc. 135 2013 6504 6512
10. J.Z. Bereszczak, N.R. Watts, P.T. Wingfield, A.C. Steven, and A.J. Heck Assessment of differences in the conformational flexibility of hepatitis B virus core-antigen and e-antigen by hydrogen deuterium exchange-mass spectrometry Protein Sci. 2014
11. C.T. Bock, S. Schwinn, S. Locarnini, J. Fyfe, M.P. Manns, C. Trautwein, and H. Zentgraf Structural organization of the hepatitis B virus minichromosome J. Mol. Biol. 307 2001 183 196
12. B. Bottcher, S.A. Wynne, and R.A. Crowther Determination of the fold of the core protein of hepatitis B virus by electron cryomicroscopy Nature 386 1997 88 91
13. C. Bourne, M.G. Finn, and A. Zlotnick Global structural changes in hepatitis B capsids induced by the assembly effector HAP1 J. Virol. 80 2006 11055 11061
14. C. Bourne, S. Lee, B. Venkataiah, A. Lee, B. Korba, M.G. Finn, and A. Zlotnick Small-Molecule Effectors of Hepatitis B Virus Capsid Assembly Give Insight into Virus Life Cycle J. Virol. 82 2008 10262 10270
15. C.R. Bourne, S.P. Katen, M.R. Fulz, C. Packianathan, and A. Zlotnick A Mutant hepatitis B virus core protein mimics inhibitors of icosahedral capsid self-assembly Biochemistry 48 2009 1736 1742
16. M.A. Buendia, and C. Neuveut Hepatocellular carcinoma Cold Spring Harb. Perspect. Med. 5 2015 a021444
17. J.S. Burg, J.R. Ingram, A.J. Venkatakrishnan, K.M. Jude, A. Dukkipati, E.N. Feinberg, A. Angelini, D. Waghray, R.O. Dror, H.L. Ploegh, and K.C. Garcia Structural biology. Structural basis for chemokine recognition and activation of a viral G protein-coupled receptor Science 347 2015 1113 1117
18. D. Cai, C. Mills, W. Yu, R. Yan, C.E. Aldrich, J.R. Saputelli, W.S. Mason, X. Xu, J.T. Guo, T.M. Block, A. Cuconati, and H. Guo Identification of disubstituted sulfonamide compounds as specific inhibitors of hepatitis B virus covalently closed circular DNA formation Antimicrob. Agents Chemother. 56 2012 4277 4288
19. M.R. Campagna, F. Liu, R. Mao, C. Mills, D. Cai, F. Guo, X. Zhao, H. Ye, A. Cuconati, H. Guo, J. Chang, X. Xu, T.M. Block, and J.T. Guo Sulfamoylbenzamide derivatives inhibit the assembly of hepatitis B virus nucleocapsids J. Virol. 87 2013 6931 6942
20. P. Ceres, S.J. Stray, and A. Zlotnick Hepatitis B virus capsid assembly is enhanced by naturally occurring mutation F97L J. Virol. 78 2004 9538 9543
21. P. Ceres, and A. Zlotnick Weak protein-protein interactions are sufficient to drive assembly of hepatitis B virus capsids Biochemistry 41 2002 11525 11531
22. C. Chen, J.C.-Y. Wang, and A. Zlotnick A kinase chaperones hepatitis B virus capsid assembly and captures capsid dynamics in vitro PLoS Pathog. 7 2011 e1002388
23. Y. Chen, and P.L. Marion Amino acids essential for RNase H activity of hepadnaviruses are also required for efficient elongation of minus-strand viral DNA J. Virol. 70 1996 6151 6156
24. P.W. Chiang, K.S. Jeng, C.P. Hu, and C.M. Chang Characterization of a cis element required for packaging and replication of the human hepatitis B virus Virology 186 1992 701 711
25. M.H. Cho, J.S. Song, H.J. Kim, S.G. Park, and G. Jung Structure-based design and biochemical evaluation of sulfanilamide derivatives as hepatitis B virus capsid assembly inhibitors J. Enzyme Inhib. Med. Chem. 28 2013 916 925
26. T.H. Chu, A.T. Liou, P.Y. Su, H.N. Wu, and C. Shih Nucleic acid chaperone activity associated with the arginine-rich domain of human hepatitis B virus core protein J. Virol. 88 2014 2530 2543
27. P.K. Chua, F.M. Tang, J.Y. Huang, C.S. Suen, and C. Shih Testing the balanced electrostatic interaction hypothesis of hepatitis B virus DNA synthesis by using an in vivo charge rebalance approach J. Virol. 84 2010 2340 2351
28. P.K. Chua, Y.M. Wen, and C. Shih Coexistence of two distinct secretion mutations (P5T and I97L) in hepatitis B virus core produces a wild-type pattern of secretion J. Virol. 77 2003 7673 7676
29. J.F. Conway, N. Cheng, A. Zlotnick, P.T. Wingfield, S.J. Stahl, and A.C. Steven Visualization of a 4-helix bundle in the hepatitis B virus capsid by cryo-electron microscopy Nature 386 1997 91 94
30. G. Cristofari, D. Ficheux, and J.L. Darlix The GAG-like protein of the yeast Ty1 retrotransposon contains a nucleic acid chaperone domain analogous to retroviral nucleocapsid proteins J. Biol. Chem. 275 2000 19210 19217
31. R.A. Crowther, N.A. Kiselev, B. Bottcher, J.A. Berriman, G.P. Borisova, V. Ose, and P. Pumpens Three-dimensional structure of hepatitis B virus core particles determined by electron cryomicroscopy Cell 77 1994 943 950
32. X. Cui, L. Ludgate, X. Ning, and J. Hu Maturation-associated destabilization of hepatitis B virus nucleocapsid J. Virol. 87 2013 11494 11503
33. H. Daub, S. Blencke, P. Habenberger, A. Kurtenbach, J. Dennenmoser, J. Wissing, A. Ullrich, and M. Cotten Identification of SRPK1 and SRPK2 as the major cellular protein kinases phosphorylating hepatitis B virus core protein J. Virol. 76 2002 8124 8137
34. W.E.t. Delaney, R. Edwards, D. Colledge, T. Shaw, P. Furman, G. Painter, and S. Locarnini Phenylpropenamide derivatives AT-61 and AT-130 inhibit replication of wild-type and lamivudine-resistant strains of hepatitis B virus in vitro Antimicrob. Agents Chemother. 46 2002 3057 3060
35. K. Deres, and H. Rubsamen-Waigmann Development of resistance and perspectives for future therapies against hepatitis B infections: lessons to be learned from HIV Infection 27 Suppl 2 1999 S45 S51
36. K. Deres, C.H. Schroder, A. Paessens, S. Goldmann, H.J. Hacker, O. Weber, T. Kramer, U. Niewohner, U. Pleiss, J. Stoltefuss, E. Graef, D. Koletzki, R.N. Masantschek, A. Reimann, R. Jaeger, R. Gross, B. Beckermann, K.H. Schlemmer, D. Haebich, and H. Rubsamen-Waigmann Inhibition of hepatitis B virus replication by drug-induced depletion of nucleocapsids Science 299 2003 893 896
37. M.S. Dhason, J.C. Wang, M.F. Hagan, and A. Zlotnick Differential assembly of Hepatitis B Virus core protein on single- and double-stranded nucleic acid suggest the dsDNA-filled core is spring-loaded Virology 430 2012 20 29
38. M.A. Dimattia, N.R. Watts, S.J. Stahl, J.M. Grimes, A.C. Steven, D.I. Stuart, and P.T. Wingfield Antigenic switching of Hepatitis B Virus by alternative dimerization of the capsid protein Structure 21 2013 133 142
39. N. Drayman, Y. Glick, O. Ben-nun-shaul, H. Zer, A. Zlotnick, D. Gerber, O. Schueler-Furman, and A. Oppenheim Pathogens use structural mimicry of native host ligands as a mechanism for host receptor engagement Cell Host Microbe 14 2013 63 73
40. K. Dryden, S. Wieland, F. Chisari, and M. Yeager Structure of native hepatitis B virus particles by electron cryomicroscopy and image reconstruction, american society for virology 21st Annual Meeting 2002 Lexington Ke pp. P20-26
41. A. Ducroux, S. Benhenda, L. Riviere, O.J. Semmes, M. Benkirane, and C. Neuveut The tudor domain protein spindlin1 is involved in intrinsic antiviral defense against incoming hepatitis B virus and herpes simplex virus type 1 PLoS Pathog. 10 2014 e1004343
42. EASL clinical practice guidelines Management of chronic hepatitis B virus infection J Hepatol 57 2012
43. G. Fallot, C. Neuveut, and M.A. Buendia Diverse roles of hepatitis B virus in liver cancer Curr. Opin. Virol. 2 2012 467 473
44. J.J. Feld, D. Colledge, V. Sozzi, R. Edwards, M. Littlejohn, and S.A. Locarnini The phenylpropenamide derivative AT-130 blocks HBV replication at the level of viral RNA packaging Antiviral Res. 76 2007 168 177
45. T. Fukuhara, T. Hosoya, S. Shimizu, K. Sumi, T. Oshiro, Y. Yoshinaka, M. Suzuki, N. Yamamoto, L.A. Herzenberg, and M. Hagiwara Utilization of host SR protein kinases and RNA-splicing machinery during viral replication Proc. Natl. Acad. Sci. U.S.A. 103 2006 11329 11333
46. A. Gallina, F. Bonelli, L. Zentilin, G. Rindi, M. Muttini, and G. Milanesi A recombinant hepatitis B core antigen polypeptide with the protamine-like domain deleted self-assembles into capsid particles but fails to bind nucleic acids J. Virol. 63 1989 4645 4652
47. E.V. Gazina, J.E. Fielding, B. Lin, and D.A. Anderson Core protein phosphorylation modulates pregenomic RNA encapsidation to different extents in human and duck hepatitis B viruses J. Virol. 74 2000 4721 4728
48. W.H. Gerlich, and W.S. Robinson Hepatitis B virus contains protein attached to the 5' terminus of its complete DNA strand Cell 21 1980 801 809
49. Gish, R.; Given, B.D.; Lai, C.-L.; Locarnini, S.; Lau, J.Y.N.; Lewis, D.L.; Schluep, T.; 2015. Chronic hepatitis B: natural history, virology, current management and a glimpse at future opportunities. Antiviral research in press.
50. R.G. Gish, A.S. Lok, T.T. Chang, R.A. de Man, A. Gadano, J. Sollano, K.H. Han, Y.C. Chao, S.D. Lee, M. Harris, J. Yang, R. Colonno, and H. Brett-Smith Entecavir therapy for up to 96 weeks in patients with HBeAg-positive chronic hepatitis B Gastroenterology 133 2007 1437 1444
51. H. Guo, R. Mao, T.M. Block, and J.T. Guo Production and function of the cytoplasmic deproteinized relaxed circular DNA of hepadnaviruses J. Virol. 84 2010 387 396
52. Y.H. Guo, Y.N. Li, J.R. Zhao, J. Zhang, and Z. Yan HBc binds to the CpG Islands of HBV cccDNA and promotes an epigenetic permissive state Epigenetics 6 2011 720 726
53. H.J. Hacker, K. Deres, M. Mildenberger, and C.H. Schroder Antivirals interacting with hepatitis B virus core protein and core mutations may misdirect capsid assembly in a similar fashion Biochem. Pharmacol. 66 2003 2273 2279
54. M.F. Hagan A theory for viral capsid assembly around electrostatic cores J. Chem. Phys. 130 2009 114902
55. K.M. Haines, and D.D. Loeb The sequence of the RNA primer and the DNA template influence the initiation of plus-strand DNA synthesis in hepatitis B virus J. Mol. Biol. 370 2007 471 480
56. Z.D. Harms, D.G. Haywood, A.R. Kneller, L. Selzer, A. Zlotnick, and S.C. Jacobson Single-particle electrophoresis in nanochannels Anal. Chem. 87 2015 699 705
57. A. Haryanto, A. Schmitz, B. Rabe, E. Gassert, A. Vlachou, and M. Kann Analysis of the nuclear localization signal of the hepatitis B virus capsid Int. Res. J. Biochem. Bioinform. 2 2012 174 185
58. J.K. Hilmer, A. Zlotnick, and B. Bothner Conformational equilibria and rates of localized motion within hepatitis B virus capsids J. Mol. Biol. 375 2008 581 594
59. S.A. Jones, and J. Hu Protein-primed terminal transferase activity of hepatitis B viru polymerase J. Virol. 87 2013 2563 2576
60. J. Jung, S.G. Hwang, Y.J. Chwae, S. Park, H.J. Shin, and K. Kim Phosphoacceptors threonine 162 and serines 170 and 178 within the carboxyl-terminal RRRS/T motif of the hepatitis B virus core protein make multiple contributions to hepatitis B virus replication J. Virol. 88 2014 8754 8767
61. M. Kann, A. Schmitz, and B. Rabe Intracellular transport of hepatitis B virus World J. Gastroenterol. 13 2007 39 47
62. M. Kann, B. Sodeik, A. Vlachou, W.H. Gerlich, and A. Helenius Phosphorylation-dependent binding of hepatitis B virus core particles to the nuclear pore complex J. Cell Biol. 145 1999 45 55
63. M. Kann, R. Thomssen, H.G. Kochel, and W.H. Gerlich Characterization of the endogenous protein kinase activity of the hepatitis B virus Arch. Virol. Suppl. 8 1993 53 62
64. S.P. Katen, S.R. Chirapu, M.G. Finn, and A. Zlotnick Trapping of Hepatitis B Virus capsid assembly intermediates by phenylpropenamide assembly accelerators ACS Chem. Biol. 5 2010 1125 1136
65. S.P. Katen, Z. Tan, S.R. Chirapu, M.G. Finn, and A. Zlotnick Assembly-directed antivirals differentially bind quasiequivalent pockets to modify hepatitis B virus capsid tertiary and quaternary structure Structure 21 2013 1406 1416
66. S.P. Katen, and A. Zlotnick Thermodynamics of virus capsid assembly Methods Enz. 455 2009 395 417
67. W.K. Kegel, and P. Schoot Pv Competing hydrophobic and screened-coulomb interactions in hepatitis B virus capsid assembly Biophys. J. 86 2004 3905 3913
68. R.W. King, S.K. Ladner, T.J. Miller, K. Zaifert, R.B. Perni, S.C. Conway, and M.J. Otto Inhibition of human hepatitis B virus replication by AT-61, a phenylpropenamide derivative, alone and in combination with (-)beta-L-2',3'-dideoxy-3'-thiacytidine Antimicrob. Agents Chemother. 42 1998 3179 3186
69. J. Kock, M. Nassal, K. Deres, H.E. Blum, and F. von Weizsacker Hepatitis B virus nucleocapsids formed by carboxy-terminally mutated core proteins contain spliced viral genomes but lack full-size DNA J. Virol. 78 2004 13812 13818
70. C. Koniger, I. Wingert, M. Marsmann, C. Rosler, J. Beck, and M. Nassal Involvement of the host DNA-repair enzyme TDP2 in formation of the covalently closed circular DNA persistence reservoir of hepatitis B viruses Proc. Natl. Acad. Sci. U.S.A. 111 2014 E4244 E4253
71. A.A. Kukreja, J.C. Wang, E. Pierson, D.Z. Keifer, L. Selzer, Z. Tan, B. Dragnea, M.F. Jarrold, and A. Zlotnick Structurally similar woodchuck and human hepadnavirus core proteins have distinctly different temperature dependences of assembly J. Virol. 88 2014 14105 14115
72. Y.T. Lan, J. Li, W. Liao, and J. Ou Roles of the three major phosphorylation sites of hepatitis B virus core protein in viral replication Virology 259 1999 342 348
73. S. Le Pogam, P.K. Chua, M. Newman, and C. Shih Exposure of RNA templates and encapsidation of spliced viral RNA are influenced by the arginine-rich domain of human hepatitis B virus core antigen (HBcAg 165-173) J. Virol. 79 2005 1871 1887
74. S. Le Pogam, and C. Shih Influence of a putative intermolecular interaction between core and the pre-S1 domain of the large envelope protein on hepatitis B virus secretion J. Virol. 76 2002 6510 6517
75. S. Le Pogam, T.T. Yuan, G.K. Sahu, S. Chatterjee, and C. Shih Low-level secretion of human hepatitis B virus virions caused by two independent, naturally occurring mutations (P5T and L60V) in the capsid protein J. Virol. 74 2000 9099 9105
76. J.G. Levin, J. Guo, I. Rouzina, and K. Musier-Forsyth Nucleic acid chaperone activity of HIV-1 nucleocapsid protein: critical role in reverse transcription and molecular mechanism Prog. Nucleic Acid Res. Mol. Biol. 80 2005 217 286
77. J.G. Levin, M. Mitra, A. Mascarenhas, and K. Musier-Forsyth Role of HIV-1 nucleocapsid protein in HIV-1 reverse transcription RNA Biol. 7 2010 754 774
78. M. Levrero, T. Pollicino, J. Petersen, L. Belloni, G. Raimondo, and M. Dandri Control of cccDNA function in hepatitis B virus infection J. Hepatol. 51 2009 581 592
79. E.B. Lewellyn, and D.D. Loeb Base pairing between cis-acting sequences contributes to template switching during plus-strand DNA synthesis in human hepatitis B virus J. Virol. 81 2007 6207 6215
80. E.B. Lewellyn, and D.D. Loeb The arginine clusters of the carboxy-terminal domain of the core protein of hepatitis B virus make pleiotropic contributions to genome replication J. Virol. 85 2011 1298 1309
81. E.B. Lewellyn, and D.D. Loeb Serine phosphoacceptor sites within the core protein of hepatitis B virus contribute to genome replication pleiotropically PLoS ONE 6 2011 e17202
82. L. Li, S.R. Chirapu, M.G. Finn, and A. Zlotnick Phase diagrams map the properties of antiviral agents directed against hepatitis B virus core assembly Antimicrob. Agents Chemother. 57 2013 1505 1508
83. W. Liao, and J.H. Ou Phosphorylation and nuclear localization of the hepatitis B virus core protein: significance of serine in the three repeated SPRRR motifs J. Virol. 69 1995 1025 1029
84. K. Liu, L. Ludgate, Z. Yuan, and J. Hu Regulation of multiple stages of hepadnavirus replication by the carboxyl-terminal domain of viral core protein Trans. J. Virol. 89 2015 2918 2930
85. J. Lucifora, S. Arzberger, D. Durantel, L. Belloni, M. Strubin, M. Levrero, F. Zoulim, O. Hantz, and U. Protzer Hepatitis B virus X protein is essential to initiate and maintain virus replication after infection J. Hepatol. 55 2011 996 1003
86. J. Lucifora, Y. Xia, F. Reisinger, K. Zhang, D. Stadler, X. Cheng, M.F. Sprinzl, H. Koppensteiner, Z. Makowska, T. Volz, C. Remouchamps, W.M. Chou, W.E. Thasler, N. Huser, D. Durantel, T.J. Liang, C. Munk, M.H. Heim, J.L. Browning, E. Dejardin, M. Dandri, M. Schindler, M. Heikenwalder, and U. Protzer Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA Science 343 2014 1221 1228
87. L. Ludgate, C. Adams, and J. Hu Phosphorylation state-dependent interactions of hepadnavirus core protein with host factors PLoS ONE 6 2011 e29566
88. L. Ludgate, X. Ning, D.H. Nguyen, C. Adams, L. Mentzer, and J. Hu Cyclin-dependent kinase 2 phosphorylates s/t-p sites in the hepadnavirus core protein C-terminal domain and is incorporated into viral capsids J. Virol. 86 2012 12237 12250
89. S.L. Martin, and F.D. Bushman Nucleic acid chaperone activity of the ORF1 protein from the mouse LINE-1 retrotransposon Mol. Cell. Biol. 21 2001 467 475
90. M. Melegari, S.K. Wolf, and R.J. Schneider Hepatitis B virus DNA replication is coordinated by core protein serine phosphorylation and HBx expression J. Virol. 79 2005 9810 9820
91. S. Menne, and P.J. Cote The woodchuck as an animal model for pathogenesis and therapy of chronic hepatitis B virus infection World journal of gastroenterology: WJG 13 2007 104 124
92. K.L. Mueller Structural Biology. Molecular "go" signals reveal their secrets Sci. Signal. 8 2015 ec57
93. J.D. Nardozzi, K. Lott, and G. Cingolani Phosphorylation meets nuclear import: a review Cell Commun. Signal 8 2010 32
94. M. Nassal The arginine-rich domain of the hepatitis B virus core protein is required for pregenome encapsidation and productive viral positive-strand DNA synthesis but not for virus assembly J. Virol. 66 1992 4107 4116
95. M. Nassal, M. Junker-Niepmann, and H. Schaller Translational inactivation of RNA function: discrimination against a subset of genomic transcripts during HBV nucleocapsid assembly Cell 63 1990 1357 1363
96. M. Nassal, and A. Rieger A bulged region of the hepatitis B virus RNA encapsidation signal contains the replication origin for discontinuous first-strand DNA synthesis J. Virol. 70 1996 2764 2773
97. M. Nassal, A. Rieger, and O. Steinau Topological analysis of the hepatitis B virus core particle by cysteine-cysteine cross-linking J. Mol. Biol. 225 1992 1013 1025
98. M. Nassal, and H. Schaller Hepatitis B virus replication-an update J. Viral. Hepat. 3 1996 217 226
99. M. Newman, P.K. Chua, F.M. Tang, P.Y. Su, and C. Shih Testing an electrostatic interaction hypothesis of hepatitis B virus capsid stability by using an in vitro capsid disassembly/reassembly system J. Virol. 83 2009 10616 10626
100. D.H. Nguyen, L. Ludgate, and J. Hu Hepatitis B virus-cell interactions and pathogenesis J. Cell. Physiol. 216 2008 289 294
101. X. Ning, D. Nguyen, L. Mentzer, C. Adams, H. Lee, R. Ashley, S. Hafenstein, and J. Hu Secretion of genome-free hepatitis B virus-single strand blocking model for virion morphogenesis of para-retrovirus PLoS Pathog. 7 2011 e1002255
102. C. Packianathan, S.P. Katen, C.E. Dann 3rd, and A. Zlotnick Conformational changes in the Hepatitis B virus core protein are consistent with a role for allostery in virus assembly J. Virol. 84 2010 1607 1615
103. A. Pairan, and V. Bruss Functional surfaces of the hepatitis B virus capsid J. Virol. 83 2009 11616 11623
104. D.H. Perlman, E.A. Berg, P.B. O'Connor, C.E. Costello, and J. Hu Reverse transcription-associated dephosphorylation of hepadnavirus nucleocapsids Proc. Natl. Acad. Sci. U.S.A. 102 2005 9020 9025
105. J.D. Perlmutter, M.R. Perkett, and M.F. Hagan Pathways for virus assembly around nucleic acids J. Mol. Biol. 2014
106. R.B. Perni, S.C. Conway, S.K. Ladner, K. Zaifert, M.J. Otto, and R.W. King Phenylpropenamide derivatives as inhibitors of hepatitis B virus replication Bioorg. Med. Chem. Lett. 10 2000 2687 2690
107. E.E. Pierson, D.Z. Keifer, L. Selzer, L.S. Lee, N.C. Contino, J.C. Wang, A. Zlotnick, and M.F. Jarrold Detection of late intermediates in virus capsid assembly by charge detection mass spectrometry J. Am. Chem. Soc. 136 2014 3536 3541
108. J.R. Pollack, and D. Ganem An RNA stem-loop structure directs hepatitis B virus genomic RNA encapsidation J. Virol. 67 1993 3254 3263
109. T. Pollicino, L. Belloni, G. Raffa, N. Pediconi, G. Squadrito, G. Raimondo, and M. Levrero Hepatitis B virus replication is regulated by the acetylation status of hepatitis B virus cccDNA-bound H3 and H4 histones Gastroenterology 130 2006 823 837
110. D. Ponsel, and V. Bruss Mapping of amino acid side chains on the surface of hepatitis B virus capsids required for envelopment and virion formation J. Virol. 77 2003 416 422
111. J.Z. Porterfield, M.S. Dhason, D.D. Loeb, M. Nassal, S.J. Stray, and A. Zlotnick Full-length hepatitis B virus core protein packages viral and heterologous RNA with similarly high levels of cooperativity J. Virol. 84 2010 7174 7184
112. J.Z. Porterfield, and A. Zlotnick A simple and general method for determining the protein and nucleic acid content of viruses by UV absorbance Virology 407 2010 281 288
113. P.E.J. Prevelige Inhibiting virus-capsid assembly by altering the polymerisation pathway Trends Biotech. 16 1998 61 65
114. G. Qian, B. Hu, D. Zhou, Y. Xuan, L. Bai, and C. Duan NIRF, a Novel Ubiquitin Ligase, Inhibits Hepatitis B Virus Replication Through Effect on HBV Core Protein and H3 Histones DNA Cell Biol. 2015
115. G. Qian, F. Jin, L. Chang, Y. Yang, H. Peng, and C. Duan NIRF, a novel ubiquitin ligase, interacts with hepatitis B virus core protein and promotes its degradation Biotechnol. Lett. 34 2012 29 36
116. L. Qin, I. Kufareva, L.G. Holden, C. Wang, Y. Zheng, C. Zhao, G. Fenalti, H. Wu, G.W. Han, V. Cherezov, R. Abagyan, R.C. Stevens, and T.M. Handel Structural biology. Crystal structure of the chemokine receptor CXCR4 in complex with a viral chemokine Science 347 2015 1117 1122
117. B. Rabe, M. Delaleau, A. Bischof, M. Foss, I. Sominskaya, P. Pumpens, C. Cazenave, M. Castroviejo, and M. Kann Nuclear entry of hepatitis B virus capsids involves disintegration to protein dimers followed by nuclear reassociation to capsids PLoS Pathog. 5 2009 e1000563
118. B. Rabe, A. Vlachou, N. Pante, A. Helenius, and M. Kann Nuclear import of hepatitis B virus capsids and release of the viral genome PNAS 100 2003 9849 9854
119. G. Radziwill, W. Tucker, and H. Schaller Mutational analysis of the hepatitis B virus P gene product: domain structure and RNase H activity J. Virol. 64 1990 613 620
120. L. Rajkowitsch, D. Chen, S. Stampfl, K. Semrad, C. Waldsich, O. Mayer, M.F. Jantsch, R. Konrat, U. Blasi, and R. Schroeder RNA chaperones, RNA annealers and RNA helicases RNA Biol. 4 2007 118 130
121. R. Ricco, and D. Kanduc Hepatitis B virus and Homo sapiens proteomewide analysis: a profusion of viral peptide overlaps in neuron-specific human proteins Biol. Targets Ther. 4 2010 75 81
122. A. Rieger, and M. Nassal Specific hepatitis B virus minus-strand DNA synthesis requires only the 5' encapsidation signal and the 3'-proximal direct repeat DR1 J. Virol. 70 1996 585 589
123. A.M. Roseman, J.A. Berriman, S.A. Wynne, P.J. Butler, and R.A. Crowther A structural model for maturation of the hepatitis B virus core Proc. Natl. Acad. Sci. U.S.A. 102 2005 15821 15826
124. A. Schmitz, A. Schwarz, M. Foss, L. Zhou, B. Rabe, J. Hoellenriegel, M. Stoeber, N. Pante, and M. Kann Nucleoporin 153 arrests the nuclear import of hepatitis B virus capsids in the nuclear basket PLoS Pathog. 6 2010 e1000741
125. F. Schodel, D. Peterson, J. Zheng, J.E. Jones, J.L. Hughes, and D.R. Milich Structure of hepatitis B virus core and e-antigen. A single precore amino acid prevents nucleocapsid assembly J. Biol. Chem. 268 1993 1332 1337
126. C. Seeger, F. Zoulim, and W.S. Mason Hepadnaviruses D.M. Knipe, D.E. Griffin, R.A. Lamb, M.A. Martin, B. Roizman, S.E. Straus, Fields Virology 2007 Lippincott Williams & Wilkins Philadelphia 2977 3029
127. S. Seitz, S. Urban, C. Antoni, and B. Bottcher Cryo-electron microscopy of hepatitis B virions reveals variability in envelope capsid interactions EMBO J. 26 2007 4160 4167
128. L. Selzer, S.P. Katen, and A. Zlotnick The hepatitis B virus core protein intradimer interface modulates capsid assembly and stability Biochemistry 53 2014 5496 5504
129. L. Shi, S. Li, F. Shen, H. Li, S. Qian, D.H. Lee, J.Z. Wu, and W. Yang Characterization of nucleosome positioning in hepadnaviral covalently closed circular DNA minichromosomes J. Virol. 86 2012 10059 10069
130. J.M. Short, S. Chen, A.M. Roseman, P.J. Butler, and R.A. Crowther Structure of hepatitis B surface antigen from subviral tubes determined by electron cryomicroscopy J. Mol. Biol. 390 2009 135 141
131. S. Singh, and A. Zlotnick Observed hysteresis of virus capsid disassembly is implicit in kinetic models of assembly J. Biol. Chem. 278 2003 18249 18255
132. L.M. Stannard, and M. Hodgkiss Morphological irregularities in Dane particle cores J. Gen. Virol. 45 1979 509 514
133. S.J. Stray, C.R. Bourne, S. Punna, W.G. Lewis, M.G. Finn, and A. Zlotnick A heteroaryldihydropyrimidine activates and can misdirect hepatitis B virus capsid assembly Proc. Natl. Acad. Sci. U.S.A. 102 2005 8138 8143
134. S.J. Stray, P. Ceres, and A. Zlotnick Zinc ions trigger conformational change and oligomerization of hepatitis B virus capsid protein Biochemistry 43 2004 9989 9998
135. S.J. Stray, and A. Zlotnick BAY 41-4109 has multiple effects on Hepatitis B virus capsid assembly J. Mol. Recognit. 19 2006 542 548
136. Z. Tan, M.L. Maguire, D.D. Loeb, and A. Zlotnick Genetically altering the thermodynamics and kinetics of hepatitis B virus capsid assembly has profound effects on virus replication in cell culture J. Virol. 87 2013 3208 3216
137. Z. Tan, K. Pionek, N. Unchwaniwala, M.L. Maguire, D.D. Loeb, and A. Zlotnick The interface between hepatitis b virus capsid proteins affects self-assembly, pregenomic RNA packaging, and reverse transcription J. Virol. 89 2015 3275 3284
138. J.E. Tavis, S. Perri, and D. Ganem Hepadnavirus reverse transcription initiates within the stem-loop of the RNA packaging signal and employs a novel strand transfer J. Virol. 68 1994 3536 3543
139. C.M. Teschke, J. King, and P.E. Prevelige Jr. Inhibition of viral capsid assembly by 1,1'-bi(4-anilinonaphthalene-5-sulfonic acid) Biochemistry 32 1993 10658 10665
140. C. Uetrecht, C. Versluis, N.R. Watts, P.T. Wingfield, A.C. Steven, and A.J. Heck Stability and shape of hepatitis B virus capsids in vacuo Angew. Chem. Int. Ed. Engl. 47 2008 6247 6251
141. G.H. Wang, and C. Seeger The reverse transcriptase of hepatitis B virus acts as a protein primer for viral DNA synthesis Cell 71 1992 663 670
142. G.H. Wang, and C. Seeger Novel mechanism for reverse transcription in hepatitis B viruses J. Virol. 67 1993 6507 6512
143. J.C. Wang, M.S. Dhason, and A. Zlotnick Structural organization of pregenomic RNA and the carboxy-terminal domain of the capsid protein of hepatitis B virus PLoS Pathog. 8 2012 e1002919
144. J.C. Wang, D.G. Nickens, T.B. Lentz, D.D. Loeb, and A. Zlotnick Encapsidated hepatitis B virus reverse transcriptase is poised on an ordered RNA lattice Proc. Natl. Acad. Sci. U.S.A. 111 2014 11329 11334
145. X.Y. Wang, Z.M. Wei, G.Y. Wu, J.H. Wang, Y.J. Zhang, J. Li, H.H. Zhang, X.W. Xie, X. Wang, Z.H. Wang, L. Wei, Y. Wang, and H.S. Chen In vitro inhibition of HBV replication by a novel compound, GLS4, and its efficacy against adefovir-dipivoxil-resistant HBV mutations Antivir. Ther. 17 2012 793 803
146. G. Wasenauer, J. Kock, and H.J. Schlicht A cysteine and a hydrophobic sequence in the noncleaved portion of the pre-C leader peptide determine the biophysical properties of the secretory core protein (HBe protein) of human hepatitis B virus J. Virol. 66 1993 5338 5346
147. N.R. Watts, J.F. Conway, N. Cheng, S.J. Stahl, A.C. Steven, and P.T. Wingfield Role of the propeptide in controlling conformation and assembly state of hepatitis B virus e-antigen J. Mol. Biol. 409 2011 202 213
148. N.R. Watts, J.G. Vethanayagam, R.B. Ferns, R.S. Tedder, A. Harris, S.J. Stahl, A.C. Steven, and P.T. Wingfield Molecular basis for the high degree of antigenic cross-reactivity between hepatitis B virus capsids (HBcAg) and dimeric capsid-related protein (HBeAg): insights into the enigmatic nature of the e-antigen J. Mol. Biol. 398 2010 530 541
149. O. Weber, K.H. Schlemmer, E. Hartmann, I. Hagelschuer, A. Paessens, E. Graef, K. Deres, S. Goldmann, U. Niewoehner, J. Stoltefuss, D. Haebich, H. Ruebsamen-Waigmann, and S. Wohlfeil Inhibition of human hepatitis B virus (HBV) by a novel non-nucleosidic compound in a transgenic mouse model Antiviral Res. 54 2002 69 78
150. H. Will, W. Reiser, T. Weimer, E. Pfaff, M. Buscher, R. Sprengel, R. Cattaneo, and H. Schaller Replication strategy of human hepatitis B virus J. Virol. 61 1987 904 911
151. M.C. Williams, R.J. Gorelick, and K. Musier-Forsyth Specific zinc-finger architecture required for HIV-1 nucleocapsid protein's nucleic acid chaperone function Proc. Natl. Acad. Sci. U.S.A. 99 2002 8614 8619
152. P.T. Wingfield, S.J. Stahl, R.W. Williams, and A.C. Steven Hepatitis core antigen produced in Escherichia coli: subunit composition, conformational analysis, and in vitro capsid assembly Biochemistry 34 1995 4919 4932
153. G. Wounderlich, and V. Bruss Characterization of early hepatitis B virus surface protein oligomers Arch. Virol. 141 1996 1191 1205
154. G. Wu, B. Liu, Y. Zhang, J. Li, A. Arzumanyan, M.M. Clayton, R.F. Schinazi, Z. Wang, S. Goldmann, Q. Ren, F. Zhang, and M.A. Feitelson Preclinical characterization of GLS4, an inhibitor of Hepatitis B virus core particle assembly Antimicrob. Agents Chemother. 57 2013 5344 5354
155. S.A. Wynne, R.A. Crowther, and A.G.W. Leslie The crystal structure of the human hepatitis B virus capsid Mol. Cell 3 1999 771 780
156. Y. Xia, J. Lucifora, K. Zhang, X. Cheng, D. Stadler, F. Reisinger, M. Feuerherd, Z. Makowska, D. Hartman, W.E. Thasler, M.H. Heim, M. Heikenwalder, and U. Protzer Interferons induce degradation of HBV CccDNA Hepatology 58 2013 274A
157. C.T. Yeh, Y.F. Liaw, and J.H. Ou The arginine-rich domain of hepatitis B virus precore and core proteins contains a signal for nuclear transport J. Virol. 64 1990 6141 6147
158. C.T. Yeh, and J.H. Ou Phosphorylation of hepatitis B virus precore and core proteins J. Virol. 65 1991 2327 2331
159. X. Yu, L. Jin, J. Jih, C. Shih, and Z.H. Zhou 3.5A cryoEM structure of hepatitis B virus core assembled from full-length core protein PLoS ONE 8 2013 e69729
160. T.T. Yuan, G.K. Sahu, W.E. Whitehead, R. Greenberg, and C. Shih The mechanism of an immature secretion phenotype of a highly frequent naturally occurring missense mutation at codon 97 of human hepatitis B virus core antigen J. Virol. 73 1999 5731 5740
161. T.T. Yuan, and C. Shih A frequent, naturally occurring mutation (P130T) of human hepatitis B virus core antigen is compensatory for immature secretion phenotype of another frequent variant (I97L) J. Virol. 74 2000 4929 4932
162. Y. Zhang, R. Mao, R. Yan, D. Cai, H. Zhu, Y. Kang, H. Liu, J. Wang, Y. Qin, Y. Huang, H. Guo, and J. Zhang Transcription of hepatitis B virus covalently closed circular DNA is regulated by CpG methylation during chronic infection PLoS ONE 9 2014 e110442
163. Y. Zheng, X.D. Fu, and J.H. Ou Suppression of hepatitis B virus replication by SRPK1 and SRPK2 via a pathway independent of the phosphorylation of the viral core protein Virology 342 2005 150 158
164. X.Y. Zhong, J.H. Ding, J.A. Adams, G. Ghosh, and X.D. Fu Regulation of SR protein phosphorylation and alternative splicing by modulating kinetic interactions of SRPK1 with molecular chaperones Genes Dev. 23 2009 482 495
165. S. Zhou, and D.N. Standring Cys residues of the hepatitis B virus capsid protein are not essential for the assembly of viral core particles but can influence their stability J. Virol. 66 1992 5393 5398
166. A. Zlotnick Are weak protein-protein interactions the general rule in capsid assembly? Virology 315 2003 269 274
167. A. Zlotnick Are weak protein-protein interactions the general rule in capsid assembly? Virology 315 2003 269 274
168. A. Zlotnick Distinguishing reversible from irreversible virus capsid assembly J. Mol. Biol. 366 2007 14 18
169. A. Zlotnick, P. Ceres, S. Singh, and J.M. Johnson A small molecule inhibits and misdirects assembly of hepatitis B virus capsids J. Virol. 76 2002 4848 4854
170. A. Zlotnick, N. Cheng, J.F. Conway, F.P. Booy, A.C. Steven, S.J. Stahl, and P.T. Wingfield Dimorphism of hepatitis B virus capsids is strongly influenced by the C-terminus of the capsid protein Biochemistry 35 1996 7412 7421
171. A. Zlotnick, N. Cheng, S.J. Stahl, J.F. Conway, A.C. Steven, and P.T. Wingfield Localization of the C terminus of the assembly domain of hepatitis B virus capsid protein: implications for morphogenesis and organization of encapsidated RNA Proc. Natl. Acad. Sci. U.S.A. 94 1997 9556 9561
172. A. Zlotnick, and B.A. Fane Mechanisms of Icosahedral Virus Assembly M. Agbandje-McKenna, R. McKenna, Structural Virology 2011 Royal Society of Chemistry London 180 202
173. A. Zlotnick, J.M. Johnson, P.W. Wingfield, S.J. Stahl, and D. Endres A theoretical model successfully identifies features of hepatitis B virus capsid assembly Biochemistry 38 1999 14644 14652
174. A. Zlotnick, and S. Mukhopadhyay Virus assembly, allostery and antivirals Trends Microbiol. 19 2011 14 23
175. A. Zlotnick, and S.J. Stray How does your virus grow? Understanding and interfering with virus assembly Trends Biotechnol. 21 2003 536 542
176. F. Zoulim, and C. Seeger Reverse transcription in hepatitis B viruses is primed by a tyrosine residue of the polymerase J. Virol. 68 1994 6 13