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Review

Understanding Capsid Assembly and Genome Packaging for Adeno-Associated Viruses

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Pages 283-297 | Received 18 Jan 2017, Accepted 15 Mar 2017, Published online: 08 Jun 2017

References

  • Gao G , VandenbergheLH, AlviraMRet al. Clades of adeno-associated viruses are widely disseminated in human tissues . J. Virol.78 ( 12 ), 6381 – 6388 ( 2004 ).
  • Weitzman MD , LindenRM . Adeno-associated virus biology . Methods Mol. Biol.807, 1 – 23 ( 2011 ).
  • Smith RH , KotinRM . The Rep52 gene product of adeno-associated virus is a DNA helicase with 3’-to-5’ polarity . J. Virol.72 ( 6 ), 4874 – 4881 ( 1998 ).
  • Cassell GD , WeitzmanMD . Characterization of a nuclear localization signal in the C-terminus of the adeno-associated virus Rep68/78 proteins . Virology327 ( 2 ), 206 – 214 ( 2004 ).
  • Redemann BE , MendelsonE, CarterBJ . Adeno-associated virus rep protein synthesis during productive infection . J. Virol.63 ( 2 ), 873 – 882 ( 1989 ).
  • Im D-S , MuzyczkaN . The AAV origin-binding protein Rep68 is an ATP-dependent site-specific endonuclease with helicase activity . Cell61, 447 – 457 ( 1990 ).
  • Girod A , WobusCE, ZadoriZet al. The VP1 capsid protein of adeno-associated virus type 2 is carrying a phospholipase A2 domain required for virus infectivity . J. Gen. Virol.83 ( Pt 5 ), 973 – 978 ( 2002 ).
  • Mclaughlin SK , CollisP, HermonatPL, MuzyczkaN . Adeno-associated virus general transduction vectors: analysis of proviral structures . J. Virol.62 ( 6 ), 1963 – 1973 ( 1988 ).
  • Nonnenmacher M , WeberT . Intracellular transport of recombinant adeno-associated virus vectors . Gene Ther.19 ( 6 ), 649 – 658 ( 2012 ).
  • Gray JT , ZolotukhinS . Design and construction of functional AAV vectors . Methods Mol. Biol.807, 25 – 46 ( 2011 ).
  • Grimm D , KayMA, KleinschmidtJA . Helper virus-free, optically controllable, and two-plasmid-based production of adeno-associated virus vectors of serotypes 1 to 6 . Mol. Ther.7 ( 6 ), 839 – 850 ( 2003 ).
  • Marsic D , ZolotukhinS . Altering Tropism of rAAV by directed evolution . Methods Mol. Biol.1382, 151 – 173 ( 2016 ).
  • Chapman MS , Agbandje-MckennaM . Atomic structure of viral particles . In : Parvoviruses . BloomME, LindenRM, ParrishCR, KerrJR ( Eds ). Edward Arnold, Ltd, London, UK, 109 – 123 ( 2006 ).
  • Buller RM , RoseJA . Characterization of adenovirus-associated virus-induced polypeptides in KB cells . J. Virol.25 ( 1 ), 331 – 338 ( 1978 ).
  • Mikals K , NamHJ, Van VlietKet al. The structure of AAVrh32.33, a novel gene delivery vector . J. Struct. Biol.186 ( 2 ), 308 – 317 ( 2014 ).
  • Govindasamy L , DiMattiaMA, GurdaBLet al. Structural insights into adeno-associated virus serotype 5 . J. Virol.87 ( 20 ), 11187 – 11199 ( 2013 ).
  • DiMattia MA , NamHJ, Van VlietKet al. Structural insight into the unique properties of adeno-associated virus serotype 9 . J. Virol.86 ( 12 ), 6947 – 6958 ( 2012 ).
  • Ng R , GovindasamyL, GurdaBLet al. Structural characterization of the dual glycan binding adeno-associated virus serotype 6 . J. Virol.84 ( 24 ), 12945 – 12957 ( 2010 ).
  • Lerch TF , XieQ, ChapmanMS . The structure ofadeno-associated virus serotype 3B (AAV-3B): insights into receptor binding and immune evasion . Virology403 ( 1 ), 26 – 36 ( 2010 ).
  • Xie Q , LerchTF, MeyerNL, ChapmanMS . Structure-function analysis of receptor-binding in adeno-associated virus serotype 6 (AAV-6) . Virology420 ( 1 ), 10 – 19 ( 2011 ).
  • Kronenberg S , BottcherB, Von Der LiethCW, BlekerS, KleinschmidtJA . A conformational change in the adeno-associated virus type 2 capsid leads to the exposure of hidden VP1 N termini . J. Virol.79 ( 9 ), 5296 – 5303 ( 2005 ).
  • Delano WL . The PyMOL Molecular Graphics System ( 2002 ). www.pymol.org/ .
  • Govindasamy L , PadronE, MckennaRet al. Structurally mapping the diverse phenotype of adeno-associated virus serotype 4 . J. Virol.80 ( 23 ), 11556 – 11570 ( 2006 ).
  • Agbandje-Mckenna M , KleinschmidtJ . AAV capsid structure and cell interactions . Methods Mol. Biol.807, 47 – 92 ( 2011 ).
  • Myers MW , CarterBJ . Assembly of adeno-associated virus . Virology102 ( 1 ), 71 – 82 ( 1980 ).
  • Wistuba A , KernA, WegerS, GrimmD, KleinschmidtJA . Subcellular compartmentalization of adeno-associated virus type 2 assembly . J. Virol.71 ( 2 ), 1341 – 1352 ( 1997 ).
  • Wistuba A , WegerS, KernA, KleinschmidtJA . Intermediates of adeno-associated virus type 2 assembly: identification of soluble complexes containing Rep and Cap proteins . J. Virol.69 ( 9 ), 5311 – 5319 ( 1995 ).
  • Johnson FB , OzerHL, HogganMD . Structural proteins of adenovirus-associated virus type 3 . J. Virol.8 ( 6 ), 860 – 863 ( 1971 ).
  • Rose JA , MaizelJVJr, InmanJK, ShatkinAJ . Structural proteins of adenovirus-associated viruses . J. Virol.8 ( 5 ), 766 – 770 ( 1971 ).
  • Snijder J , van de WaterbeemdM, DamocEet al. Defining the stoichiometry and cargo load of viral and bacterial nanoparticles by Orbitrap mass spectrometry . J. Am. Chem. Soc.136 ( 20 ), 7295 – 7299 ( 2014 ).
  • Ruffing M , ZentgrafH, KleinschmidtJA . Assembly of viruslike particles by recombinant structural proteins of adeno-associated virus type 2 in insect cells . J. Virol.66 ( 12 ), 6922 – 6930 ( 1992 ).
  • Steinbach S , WistubaA, BockT, KleinschmidtJA . Assembly of adeno-associated virus type 2 capsids in vitro . J. Gen. Virol.78 ( Pt 6 ), 1453 – 1462 ( 1997 ).
  • Rabinowitz JE , XiaoW, SamulskiRJ . Insertional mutagenesis of AAV2 capsid and the production of recombinant virus . Virology265 ( 2 ), 274 – 285 ( 1999 ).
  • Warrington KH Jr , GorbatyukOS, HarrisonJK, OpieSR, ZolotukhinS, MuzyczkaN . Adeno-associated virus type 2 VP2 capsid protein is nonessential and can tolerate large peptide insertions at its N terminus . J. Virol.78 ( 12 ), 6595 – 6609 ( 2004 ).
  • Sonntag F , SchmidtK, KleinschmidtJA . A viral assembly factor promotes AAV2 capsid formation in the nucleolus . Proc. Natl Acad. Sci. USA107 ( 22 ), 10220 – 10225 ( 2010 ).
  • Bleker S , SonntagF, KleinschmidtJA . Mutational analysis of narrow pores at the fivefold symmetry axes of adeno-associated virus type 2 capsids reveals a dual role in genome packaging and activation of phospholipase A2 activity . J. Virol.79 ( 4 ), 2528 – 2540 ( 2005 ).
  • Popa-Wagner R , PorwalM, KannMet al. Impact of VP1-specific protein sequence motifs on adeno-associated virus type 2 intracellular trafficking and nuclear entry . J. Virol.86 ( 17 ), 9163 – 9174 ( 2012 ).
  • Wu P , XiaoW, ConlonTet al. Mutational analysis of the adeno-associated virus type 2 (AAV2) capsid gene and construction of AAV2 vectors with altered tropism . J. Virol.74 ( 18 ), 8635 – 8647 ( 2000 ).
  • Naumer M , SonntagF, SchmidtKet al. Properties of the adeno-associated virus assembly-activating protein . J. Virol.86 ( 23 ), 13038 – 13048 ( 2012 ).
  • Grieger JC , SnowdyS, SamulskiRJ . Separate basic region motifs within the adeno-associated virus capsid proteins are essential for infectivity and assembly . J. Virol.80 ( 11 ), 5199 – 5210 ( 2006 ).
  • Hunter LA , SamulskiRJ . Colocalization of adeno-associated virus Rep and capsid proteins in the nuclei of infected cells . J. Virol.66 ( 1 ), 317 – 324 ( 1992 ).
  • Bleker S , PawlitaM, KleinschmidtJA . Impact of capsid conformation and Rep-capsid interactions on adeno-associated virus type 2 genome packaging . J. Virol.80 ( 2 ), 810 – 820 ( 2006 ).
  • Bevington JM , NeedhamPG, VerrillKC, CollacoRF, BasrurV, TrempeJP . Adeno-associated virus interactions with B23/Nucleophosmin: identification of sub-nucleolar virion regions . Virology357 ( 1 ), 102 – 113 ( 2007 ).
  • Qiu J , BrownKE . A 110-kDa nuclear shuttle protein, nucleolin, specifically binds to adeno-associated virus type 2 (AAV-2) capsid . Virology257 ( 2 ), 373 – 382 ( 1999 ).
  • Earley LF , PowersJM, AdachiKet al. Adeno-associated virus assembly-activating protein is not an essential requirement for capsid assembly of AAV serotypes 4, 5 and 11 . J. Virol.85 ( 23 ), 12686 – 12697 ( 2016 ).
  • Sonntag F , KotherK, SchmidtKet al. The assembly-activating protein promotes capsid assembly of different adeno-associated virus serotypes . J. Virol.85 ( 23 ), 12686 – 12697 ( 2011 ).
  • Popa-Wagner R , SonntagF, SchmidtK, KingJ, KleinschmidtJA . Nuclear translocation of adeno-associated virus type 2 capsid proteins for virion assembly . J. Gen. Virol.93 ( Pt 9 ), 1887 – 1898 ( 2012 ).
  • Mayor HD , TorikaiK, MelnickJL, MandelM . Plus and minus single-stranded DNA separately encapsidated in adeno-associated satellite virions . Science166 ( 3910 ), 1280 – 1282 ( 1969 ).
  • Ling C , WangY, LuYet al. Enhanced transgene expression from recombinant single-stranded D-sequence-substituted adeno-associated virus vectors in human cell lines in vitro and in murine hepatocytes in vivo . J. Virol.89 ( 2 ), 952 – 961 ( 2015 ).
  • Wang XS , QingK, PonnazhaganS, SrivastavaA . Adeno-associated virus type 2 DNA replication in vivo: mutation analyses of the D sequence in viral inverted terminal repeats . J. Virol.71 ( 4 ), 3077 – 3082 ( 1997 ).
  • Alex M , WegerS, MietzschM, SlaninaH, CathomenT, HeilbronnR . DNA-binding activity of adeno-associated virus Rep is required for inverted terminal repeat-dependent complex formation with herpes simplex virus ICP8 . J. Virol.86 ( 5 ), 2859 – 2863 ( 2012 ).
  • Im DS , MuzyczkaN . Factors that bind to adeno-associated virus terminal repeats . J. Virol.63 ( 7 ), 3095 – 3104 ( 1989 ).
  • King JA , DubielzigR, GrimmD, KleinschmidtJA . DNA helicase-mediated packaging of adeno-associated virus type 2 genomes into preformed capsids . Embo. J.20 ( 12 ), 3282 – 3291 ( 2001 ).
  • Yoon-Robarts M , BlouinAG, BlekerSet al. Residues within the B’ motif are critical for DNA binding by the superfamily 3 helicase Rep40 of adeno-associated virus type 2 . J. Biol. Chem.279 ( 48 ), 50472 – 50481 ( 2004 ).
  • Dubielzig R , KingJA, WegerS, KernA, KleinschmidtJA . Adeno-associated virus type 2 protein interactions: formation of pre-encapsidation complexes . J. Virol.73 ( 11 ), 8989 – 8998 ( 1999 ).
  • Drouin LM , LinsB, JanssenMet al. Cryo-electron microscopy reconstruction and stability studies of the wild type and the R432A variant of adeno-associated virus type 2 reveal that capsid structural stability is a major factor in genome packaging . J. Virol.90 ( 19 ), 8542 – 8551 ( 2016 ).
  • Cotmore SF , D’abramo AMJr, TicknorCM, TattersallP . Controlled conformational transitions in the MVM virion expose the VP1 N-terminus and viral genome without particle disassembly . Virology254 ( 1 ), 169 – 181 ( 1999 ).
  • Cotmore SF , TattersallP . Encapsidation of minute virus of mice DNA: aspects of the translocation mechanism revealed by the structure of partially packaged genomes . Virology336 ( 1 ), 100 – 112 ( 2005 ).
  • Nam HJ , LaneMD, PadronEet al. Structure of adeno-associated virus serotype 8, a gene therapy vector . J. Virol.81 ( 22 ), 12260 – 12271 ( 2007 ).
  • Halder S , Van VlietK, SmithJKet al. Structure of neurotropic adeno-associated virus AAVrh.8 . J. Struct. Biol.192 ( 1 ), 21 – 36 ( 2015 ).
  • Mikals K , NamHJ, Van VlietKet al. The structure of AAVrh32.33, a novel gene delivery vector . J. Struct. Biol.186 ( 2 ), 308 – 317 ( 2014 ).
  • Dong JY , FanPD, FrizzellRA . Quantitative analysis of the packaging capacity of recombinant adeno-associated virus . Hum. Gene Ther.7 ( 17 ), 2101 – 2112 ( 1996 ).
  • Wu Z , YangH, ColosiP . Effect of genome size on AAV vector packaging . Mol. Ther.18 ( 1 ), 80 – 86 ( 2010 ).
  • Grieger JC , SamulskiRJ . Packaging capacity of adeno-associated virus serotypes: impact of larger genomes on infectivity and postentry steps . J. Virol.79 ( 15 ), 9933 – 9944 ( 2005 ).
  • Hirsch ML , Agbandje-MckennaM, SamulskiRJ . Little vector, big gene transduction: fragmented genome reassembly of adeno-associated virus . Mol. Ther.18 ( 1 ), 6 – 8 ( 2010 ).
  • Gray SJ , FotiSB, SchwartzJWet al. Optimizing promoters for recombinant adeno-associated virus-mediated gene expression in the peripheral and central nervous system using self-complementary vectors . Hum. Gene Ther.22 ( 9 ), 1143 – 1153 ( 2011 ).
  • Choi JH , YuNK, BaekGCet al. Optimization of AAV expression cassettes to improve packaging capacity and transgene expression in neurons . Mol. Brain7, 17 ( 2014 ).
  • Ostedgaard LS , RokhlinaT, KarpPHet al. A shortened adeno-associated virus expression cassette for CFTR gene transfer to cystic fibrosis airway epithelia . Proc. Natl Acad. Sci. USA102 ( 8 ), 2952 – 2957 ( 2005 ).
  • Palfi A , ChaddertonN, MckeeAGet al. Efficacy of codelivery of dual AAV2/5 vectors in the murine retina and hippocampus . Hum. Gene Ther.23 ( 8 ), 847 – 858 ( 2012 ).
  • Allocca M , DoriaM, PetrilloMet al. Serotype-dependent packaging of large genes in adeno-associated viral vectors results in effective gene delivery in mice . J. Clin. Invest.118 ( 5 ), 1955 – 1964 ( 2008 ).
  • Ghosh A , YueY, LaiY, DuanD . A hybrid vector system expands adeno-associated viral vector packaging capacity in a transgene-independent manner . Mol. Ther.16 ( 1 ), 124 – 130 ( 2008 ).
  • Hirsch ML , LiC, BellonIet al. Oversized AAV transductifon is mediated via a DNA-PKcs-independent, Rad51C-dependent repair pathway . Mol. Ther.21 ( 12 ), 2205 – 2216 ( 2013 ).
  • Trapani I , ColellaP, SommellaAet al. Effective delivery of large genes to the retina by dual AAV vectors . EMBO Mol. Med.6 ( 2 ), 194 – 211 ( 2014 ).
  • Odom GL , GregorevicP, AllenJM, ChamberlainJS . Gene therapy of mdx mice with large truncated dystrophins generated by recombination using rAAV6 . Mol. Ther.19 ( 1 ), 36 – 45 ( 2011 ).
  • Yan Z , ZhangY, DuanD, EngelhardtJF . Trans-splicing vectors expand the utility of adeno-associated virus for gene therapy . Proc. Natl Acad. Sci. USA97 ( 12 ), 6716 – 6721 ( 2000 ).
  • Koo T , PopplewellL, AthanasopoulosT, DicksonG . Triple trans-splicing adeno-associated virus vectors capable of transferring the coding sequence for full-length dystrophin protein into dystrophic mice . Hum. Gene Ther.25 ( 2 ), 98 – 108 ( 2014 ).
  • Bowles DE , McpheeSW, LiCet al. Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector . Mol. Ther.20 ( 2 ), 443 – 455 ( 2012 ).
  • Mccarty DM , MonahanPE, SamulskiRJ . Self-complementary recombinant adeno-associated virus (scAAV) vectors promote efficient transduction independently of DNA synthesis . Gene Ther.8 ( 16 ), 1248 – 1254 ( 2001 ).
  • Gao GP , LuY, SunXet al. High-level transgene expression in nonhuman primate liver with novel adeno-associated virus serotypes containing self-complementary genomes . J. Virol.80 ( 12 ), 6192 – 6194 ( 2006 ).
  • Ren C , KumarS, ShawDR, PonnazhaganS . Genomic stability of self-complementary adeno-associated virus 2 during early stages of transduction in mouse muscle in vivo . Hum. Gene Ther.16 ( 9 ), 1047 – 1057 ( 2005 ).
  • Levy HC , BowmanVD, GovindasamyLet al. Heparin binding induces conformational changes in Adeno-associated virus serotype 2 . J. Struct. Biol.165 ( 3 ), 146 – 156 ( 2009 ).
  • Hüser D , WegerS, HeilbronnR . Packaging of human chromosome 19-specific adeno-associated virus (AAV) integration sites in AAV virions during AAV wild-type and recombinant AAV vector production . J. Virol.77 ( 8 ), 4881 – 4887 ( 2003 ).
  • Nony P , ChadeufG, TessierJ, MoullierP, SalvettiA . Evidence for packaging of rep-cap sequences into adeno-associated virus (AAV) type 2 capsids in the absence of inverted terminal repeats: a model for generation of rep-positive AAV particles . J. Virol.77 ( 1 ), 776 – 781 ( 2003 ).
  • Wright JF . Manufacturing and characterizing AAV-based vectors for use in clinical studies . Gene Ther.15 ( 11 ), 840 – 848 ( 2008 ).
  • Mietzsch M , CasteleynV, WegerS, ZolotukhinS, HeilbronnR . OneBac 2.0: Sf9 cell lines for production of AAV5 vectors with enhanced infectivity and minimal encapsidation of foreign DNA . Hum. Gene Ther.26 ( 10 ), 688 – 697 ( 2015 ).
  • Hauck B , MurphySL, SmithPHet al. Undetectable transcription of cap in a clinical AAV vector: implications for preformed capsid in immune responses . Mol. Ther.17 ( 1 ), 144 – 152 ( 2009 ).
  • Lecomte E , TournaireB, CogneBet al. Advanced characterization of DNA molecules in rAAV vector preparations by single-stranded virus next-generation sequencing . Mol. Ther. Nucleic Acids4, e260 ( 2015 ).

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