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Assembly and Architecture of HIV

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Viral Molecular Machines

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 726))

Abstract

HIV forms spherical, membrane-enveloped, pleomorphic virions, 1,000–1,500 Å in diameter, which contain two copies of its single-stranded, positive-sense RNA genome. Virus particles initially bud from host cells in a noninfectious or immature form, in which the genome is further encapsulated inside a spherical protein shell composed of around 2,500 copies of the virally encoded Gag polyprotein. The Gag molecules are radially arranged, adherent to the inner leaflet of the viral membrane, and closely associated as a hexagonal, paracrystalline lattice. Gag comprises three major structural domains called MA, CA, and NC. For immature virions to become infectious, they must undergo a maturation process that is initiated by proteolytic processing of Gag by the viral protease. The new Gag-derived proteins undergo dramatic rearrangements to form the mature virus. The mature MA protein forms a “matrix” layer and remains attached to the viral envelope, NC condenses with the genome, and approximately 1,500 copies of CA assemble into a new cone-shaped protein shell, called the mature capsid, which surrounds the genomic ribonucleoprotein complex. The HIV capsid conforms to the mathematical principles of a fullerene shell, in which the CA subunits form about 250 CA hexamers arrayed on a variably curved hexagonal lattice, which is closed by incorporation of exactly 12 pentamers, seven pentamers at the wide end and five at the narrow end of the cone. This chapter describes our current understanding of HIV’s virion architecture and its dynamic transformations: the process of virion assembly as orchestrated by Gag, the architecture of the immature virion, the virus maturation process, and the structure of the mature capsid.

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Abbreviations

HIV-1:

Human immunodeficiency virus type 1

HTLV:

Human T-cell leukemia virus

MLV:

Murine leukemia virus

MPMV:

Mason-Pfizer monkey virus

RSV:

Rous sarcoma virus

References

  • Accola MA, Höglund S, Göttlinger HG (1998) A putative α-helical structure which overlaps the capsid-p2 boundary in the human immunodeficiency virus type 1 Gag precursor is crucial for viral particle assembly. J Virol 72:2072–2078

    PubMed  CAS  Google Scholar 

  • Alcaraz LA, del Álamo M, Barrera FN et al (2007) Flexibility in HIV-1 assembly subunits: solution structure of the monomeric C-terminal domain of the capsid protein. Biophys J 93:1264–1276

    PubMed  CAS  Google Scholar 

  • Aloia RC, Tian H, Jensen FC (1993) Lipid composition and fluidity of the human immunodeficiency virus envelope and host cell plasma membranes. Proc Natl Acad Sci USA 90:5181–5185

    PubMed  CAS  Google Scholar 

  • Bailey GD, Hyun JK, Mitra AK et al (2009) Proton-linked dimerization of a retroviral capsid protein initiates capsid assembly. Structure 17:737–748

    PubMed  CAS  Google Scholar 

  • Bajorek M, Schubert HL, McCullough J et al (2009) Structural basis for ESCRT-III protein autoinhibition. Nat Struct Mol Biol 16:754–762

    PubMed  CAS  Google Scholar 

  • Bartonova V, Igonet S, Sticht J et al (2008) Residues in the HIV-1 capsid assembly inhibitor binding site are essential for maintaining the assembly-competent quaternary structure of the capsid protein. J Biol Chem 283:32024–32033

    PubMed  CAS  Google Scholar 

  • Benjamin J, Ganser-Pornillos BK, Tivol WF et al (2005) Three-dimensional structure of HIV-1 virus-like particles by electron cryotomography. J Mol Biol 346:577–588

    PubMed  CAS  Google Scholar 

  • Bouamr F, Melillo JA, Wang MQ et al (2003) PPPYEPTAP motif is the late domain of human T-cell leukemia virus type 1 Gag and mediates its functional interaction with cellular proteins Nedd4 and Tsg101. J Virol 77:11882–11895

    PubMed  CAS  Google Scholar 

  • Bowzard JB, Wills JW, Craven RC (2001) Second-site suppressors of Rous sarcoma virus CA mutations: evidence for interdomain interactions. J Virol 75:6850–6856

    PubMed  CAS  Google Scholar 

  • Briggs JAG, Wilk T, Welker R et al (2003) Structural organization of authentic, mature HIV-1 virions and cores. EMBO J 22:1707–1715

    PubMed  CAS  Google Scholar 

  • Briggs JA, Grünewald K, Glass B et al (2006) The mechanism of HIV-1 core assembly: insights from three-dimensional reconstructions of authentic virions. Structure 14:15–20

    PubMed  CAS  Google Scholar 

  • Briggs JAG, Riches JD, Glass B et al (2009) Structure and assembly of immature HIV. Proc Natl Acad Sci USA 106:11090–11095

    PubMed  CAS  Google Scholar 

  • Brown DA, London E (1997) Structure of detergent-resistant membrane domains: does phase separation occur in biological membranes? Biochem Biophys Res Commun 240:1–7

    PubMed  CAS  Google Scholar 

  • Brügger B, Glass B, Haberkant P et al (2006) The HIV lipidome: a raft with an unusual composition. Proc Natl Acad Sci USA 103:2641–2646

    PubMed  Google Scholar 

  • Butan C, Winkler DC, Heymann JB et al (2008) RSV capsid polymorphism correlates with polymerization efficiency and envelope glycoprotein content: implications that nucleation controls morphogenesis. J Mol Biol 376:1168–1181

    PubMed  CAS  Google Scholar 

  • Byeon I-JL, Meng X, Jung J et al (2009) Structural convergence between cryo-EM and NMR reveals intersubunit interactions critical for HIV-1 capsid function. Cell 139:780–790

    PubMed  CAS  Google Scholar 

  • Campbell S, Rein A (1999) In vitro assembly properties of human immunodeficiency virus type 1 Gag protein lacking the p6 domain. J Virol 73:2270–2279

    PubMed  CAS  Google Scholar 

  • Campbell S, Vogt VM (1995) Self-assembly in vitro of purified CA-NC proteins from Rous sarcoma virus and human immunodeficiency virus type 1. J Virol 69:6487–6497

    PubMed  CAS  Google Scholar 

  • Campbell S, Vogt VM (1997) In vitro assembly of virus-like particles with Rous sarcoma virus Gag deletion mutants: identification of the p10 domain as a morphological determinant in the formation of spherical particles. J Virol 71:4425–4435

    PubMed  CAS  Google Scholar 

  • Campbell S, Fisher RJ, Towler EM et al (2001) Modulation of HIV-like particle assembly in vitro by inositol phosphates. Proc Natl Acad Sci USA 98:10875–10879

    PubMed  CAS  Google Scholar 

  • Campos-Olivas R, Newman JL, Summers MF (2000) Solution structure and dynamics of the Rous sarcoma virus capsid protein and comparison with capsid proteins of other retroviruses. J Mol Biol 296:633–649

    PubMed  CAS  Google Scholar 

  • Cardone G, Purdy JG, Cheng N et al (2009) Visualization of a missing link in retrovirus capsid assembly. Nature 457:694–698

    PubMed  CAS  Google Scholar 

  • Carlson L-A, Briggs JAG, Glass B et al (2008) Three-dimensional analysis of budding sites and released virus suggests a revised model for HIV-1 morphogenesis. Cell Host Microbe 4:592–599

    PubMed  CAS  Google Scholar 

  • Carlton JG, Martin-Serrano J (2007) Parallels between cytokinesis and retroviral budding: a role for the ESCRT machinery. Science 316:1908–1912

    PubMed  CAS  Google Scholar 

  • Caspar DLD, Klug A (1962) Physical principles in the construction of regular viruses. Cold Spring Harb Symp Quant Biol 27:1–24

    PubMed  CAS  Google Scholar 

  • Cheslock SR, Poon DTK, Fu W et al (2003) Charged assembly helix motif in murine leukemia virus capsid: an important region for virus assembly and particle size determination. J Virol 77:7058–7066

    PubMed  CAS  Google Scholar 

  • Chung H-Y, Morita E, von Schwedler U et al (2008) NEDD4L overexpression rescues the release and infectivity of human immunodeficiency virus type 1 constructs lacking PTAP and YPXL late domains. J Virol 82:4884–4897

    PubMed  CAS  Google Scholar 

  • Dalton AK, Murray PS, Murray D et al (2005) Biochemical characterization of rous sarcoma virus MA protein interaction with membranes. J Virol 79:6227–6238

    PubMed  CAS  Google Scholar 

  • Dalton AK, Ako-Adjei D, Murray PS et al (2007) Electrostatic interactions drive membrane association of the human immunodeficiency virus type 1 Gag MA domain. J Virol 81:6434–6445

    PubMed  CAS  Google Scholar 

  • Datta SAK, Curtis JE, Ratcliff W et al (2007a) Conformation of the HIV-1 Gag protein in solution. J Mol Biol 365:812–824

    PubMed  CAS  Google Scholar 

  • Datta SAK, Zhao Z, Clark PK et al (2007b) Interactions between HIV-1 Gag molecules in solution: an inositol phosphate-mediated switch. J Mol Biol 365:799–811

    PubMed  CAS  Google Scholar 

  • de Marco A, Davey NE, Ulbrich P et al (2010) Conserved and variable features of Gag structure and arrangement in immature retrovirus particles. J Virol 84:11729–11736

    PubMed  Google Scholar 

  • Dey A, York D, Smalls-Mantey A et al (2005) Composition and sequence-dependent binding of RNA to the nucleocapsid protein of Moloney murine leukemia virus. Biochemistry 44:3735–3744

    PubMed  CAS  Google Scholar 

  • Dorfman T, Mammano F, Haseltine WA et al (1994) Role of the matrix protein in the virion association of the human immunodeficiency virus type 1 envelope glycoprotein. J Virol 68:1689–1696

    PubMed  CAS  Google Scholar 

  • Dryden KA, Wieland SF, Whitten-Bauer C et al (2006) Native Hepatitis B virions and capsids visualized by electron cryomicroscopy. Mol Cell 22:843–850

    PubMed  CAS  Google Scholar 

  • D’Souza V, Summers MF (2004) Structural basis for packaging the dimeric genome of Moloney murine leukaemia virus. Nature 431:586–590

    PubMed  Google Scholar 

  • D’Souza V, Melamed J, Habib D et al (2001) Identification of a high affinity nucleocapsid protein binding element within the Moloney murine leukemia virus Ψ-RNA packaging signal: implications for genome recognition. J Mol Biol 314:217–232

    PubMed  Google Scholar 

  • Ehrlich LS, Agresta BE, Carter CA (1992) Assembly of recombinant human immunodeficiency virus type 1 capsid protein in vitro. J Virol 66:4874–4883

    PubMed  CAS  Google Scholar 

  • Fabrikant G, Lata S, Riches JD et al (2009) Computational model of membrane fission catalyzed by ESCRT-III. PLoS Comput Biol 5:e1000575

    PubMed  Google Scholar 

  • Forshey BM, von Schwedler U, Sundquist WI et al (2002) Formation of a human immunodeficiency virus type 1 core of optimal stability is crucial for viral replication. J Virol 76:5667–5677

    PubMed  CAS  Google Scholar 

  • Freed EO, Martin MA (1995) Virion incorporation of envelope glycoproteins with long but not short cytoplasmic tails is blocked by specific, single amino acid substitutions in the human immunodeficiency virus type 1 matrix. J Virol 69:1984–1989

    PubMed  CAS  Google Scholar 

  • Freed EO, Martin MA (1996) Domains of the human immunodeficiency virus type 1 matrix and gp41 cytoplasmic tail required for envelope incorporation into virions. J Virol 70:341–351

    PubMed  CAS  Google Scholar 

  • Fu W, Rein A (1993) Maturation of dimeric viral RNA of Moloney murine leukemia virus. J Virol 67:5443–5449

    PubMed  CAS  Google Scholar 

  • Fuller SD, Wilk T, Gowen BE et al (1997) Cryo-electron microscopy reveals ordered domains in the immature HIV-1 particle. Curr Biol 7:729–738

    PubMed  CAS  Google Scholar 

  • Gamble TR, Yoo S, Vajdos FF et al (1997) Structure of the carboxyl-terminal dimerization domain of the HIV-1 capsid protein. Science 278:849–853

    PubMed  CAS  Google Scholar 

  • Ganser BK, Li S, Klishko VY et al (1999) Assembly and analysis of conical models for the HIV-1 core. Science 283:80–83

    PubMed  CAS  Google Scholar 

  • Ganser-Pornillos BK, von Schwedler UK, Stray KM et al (2004) Assembly properties of the human immunodeficiency virus type 1 CA protein. J Virol 78:2545–2552

    PubMed  CAS  Google Scholar 

  • Ganser-Pornillos BK, Cheng A, Yeager M (2007) Structure of full-length HIV-1 CA: a model for the mature capsid lattice. Cell 131:70–79

    PubMed  CAS  Google Scholar 

  • Ganser-Pornillos BK, Yeager M, Sundquist WI (2008) The structural biology of HIV assembly. Curr Opin Struct Biol 18:203–217

    PubMed  CAS  Google Scholar 

  • Garrus JE, von Schwedler UK, Pornillos O et al (2001) Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding. Cell 107:55–65

    PubMed  CAS  Google Scholar 

  • Ghazi-Tabatabai S, Saksena S, Short JM et al (2008) Structure and disassembly of filaments formed by the ESCRT-III subunit Vps24. Structure 16:1345–1356

    PubMed  CAS  Google Scholar 

  • Gherghe C, Lombo T, Leonard CW et al (2010) Definition of a high-affinity Gag recognition structure mediating packaging of a retroviral RNA genome. Proc Natl Acad Sci USA 107:19248–19253

    PubMed  CAS  Google Scholar 

  • Gheysen D, Jacobs E, de Foresta F et al (1989) Assembly and release of HIV-1 precursor Pr55gag virus-like particles from recombinant baculovirus-infected insect cells. Cell 59:103–112

    PubMed  CAS  Google Scholar 

  • Gitti RK, Lee BM, Walker J et al (1996) Structure of the amino-terminal core domain of the HIV-1 capsid protein. Science 273:231–235

    PubMed  CAS  Google Scholar 

  • Göttlinger HG, Sodroski JG, Haseltine WA (1989) Role of capsid precursor processing and myristoylation in morphogenesis and infectivity of human immunodeficiency virus type 1. Proc Natl Acad Sci USA 86:5781–5785

    PubMed  Google Scholar 

  • Göttlinger HG, Dorfman T, Sodroski JG et al (1991) Effect of mutations affecting the p6 gag protein on human immunodeficiency virus particle release. Proc Natl Acad Sci USA 88:3195–3199

    PubMed  Google Scholar 

  • Gross I, Hohenberg H, Kräusslich H-G (1997) In vitro assembly properties of purified bacterially expressed capsid proteins of human immunodeficiency virus. Eur J Biochem 249:592–600

    PubMed  CAS  Google Scholar 

  • Gross I, Hohenberg H, Huckhagel C et al (1998) N-terminal extension of human immunodeficiency virus capsid protein converts the in vitro assembly phenotype from tubular to spherical particles. J Virol 72:4798–4810

    PubMed  CAS  Google Scholar 

  • Gross I, Hohenberg H, Wilk T et al (2000) A conformational switch controlling HIV-1 morphogenesis. EMBO J 19:103–113

    PubMed  CAS  Google Scholar 

  • Grünewald K, Desai P, Winkler DC et al (2003) Three-dimensional structure of herpes simplex virus from cryo-electron tomography. Science 302:1396–1398

    PubMed  Google Scholar 

  • Hanson PI, Roth R, Lin Y et al (2008) Plasma membrane deformation by circular arrays of ESCRT-III protein filaments. J Cell Biol 180:389–402

    PubMed  CAS  Google Scholar 

  • Hermida-Matsumoto L, Resh MD (2000) Localization of human immunodeficiency virus type 1 Gag and Env at the plasma membrane by confocal imaging. J Virol 74:8670–8679

    PubMed  CAS  Google Scholar 

  • Heymann JB, Butan C, Winkler DC et al (2008) Irregular and semi-regular polyhedral models for Rous sarcoma virus cores. Comput Math Methods Med 9:197–210

    PubMed  Google Scholar 

  • Hill CP, Worthylake D, Bancroft DP et al (1996) Crystal structures of the trimeric human immunodeficiency virus type 1 matrix protein: implications for membrane association and assembly. Proc Natl Acad Sci USA 93:3099–3104

    PubMed  CAS  Google Scholar 

  • Hurley JH, Emr SD (2006) The ESCRT complexes: structure and mechanism of a membrane-trafficking network. Annu Rev Biophys Biomol Struct 35:277–298

    PubMed  CAS  Google Scholar 

  • Hyun J-K, Radjainia M, Kingston RL et al (2010) Proton-driven assembly of the Rous Sarcoma virus capsid protein results in the formation of icosahedral particles. J Biol Chem 285:15056–15064

    PubMed  CAS  Google Scholar 

  • Ivanchenko S, Godinez WJ, Lampe M et al (2009) Dynamics of HIV-1 assembly and release. PLoS Pathog 5:e1000652

    PubMed  Google Scholar 

  • Ivanov D, Tsodikov OV, Kasanov J et al (2007) Domain-swapped dimerization of the HIV-1 capsid C-terminal domain. Proc Natl Acad Sci USA 104:4353–4358

    PubMed  CAS  Google Scholar 

  • Jin Z, Jin L, Peterson DL et al (1999) Model for lentivirus capsid core assembly based on crystal dimers of EIAV p26. J Mol Biol 286:83–93

    PubMed  CAS  Google Scholar 

  • Joint United Nations Programme on HIV/AIDS (2009) AIDS epidemic update. UNAIDS, Geneva

    Google Scholar 

  • Joshi SM, Vogt VM (2000) Role of the Rous sarcoma virus p10 domain in shape determination of Gag virus-like particles assembled in vitro and within Escherichia coli. J Virol 74:10260–10268

    PubMed  CAS  Google Scholar 

  • Jouvenet N, Bieniasz PD, Simon SM (2008) Imaging the biogenesis of individual HIV-1 virions in live cells. Nature 454:236–240

    PubMed  CAS  Google Scholar 

  • Jouvenet N, Simon SM, Bieniasz PD (2009) Imaging the interaction of HIV-1 genomes and Gag during assembly of individual viral particles. Proc Natl Acad Sci USA 106:19114–19119

    PubMed  CAS  Google Scholar 

  • Keller PW, Johnson MC, Vogt VM (2008) Mutations in the spacer peptide and adjoining sequences in Rous sarcoma virus Gag lead to tubular budding. J Virol 82:6788–6797

    PubMed  CAS  Google Scholar 

  • Keller PW, Adamson CS, Heymann JB et al (2011) HIV-1 maturation inhibitor bevirimat stabilizes the immature Gag lattice. J Virol 85:1420–1428

    PubMed  CAS  Google Scholar 

  • Kelly BN, Howard BR, Wang H et al (2006) Implications for viral capsid assembly from crystal structures of HIV-1 Gag1-278 and CA N133-278 . Biochemistry 45:11257–11266

    PubMed  CAS  Google Scholar 

  • Khorasanizadeh S, Campos-Olivas R, Summers MF (1999) Solution structure of the capsid protein from the human T-cell leukemia virus type-I. J Mol Biol 291:491–505

    PubMed  CAS  Google Scholar 

  • Kikonyogo A, Bouamr F, Vana ML et al (2001) Proteins related to the Nedd4 family of ubiquitin protein ligases interact with the L domain of Rous sarcoma virus and are required for gag budding from cells. Proc Natl Acad Sci USA 98:11199–11204

    PubMed  CAS  Google Scholar 

  • Kingston RL, Fitzon-Ostendorp T, Eisenmesser EZ et al (2000) Structure and self-association of the Rous sarcoma virus capsid protein. Structure 8:617–628

    PubMed  CAS  Google Scholar 

  • Knejzlík Z, Smékalová Z, Ruml T et al (2007) Multimerization of the p12 domain is necessary for Mason-Pfizer monkey virus Gag assembly in vitro. Virology 365:260–270

    PubMed  Google Scholar 

  • Kräusslich H-G (1991) Human immunodeficiency virus proteinase dimer as component of the viral polyprotein prevents particle assembly and viral infectivity. Proc Natl Acad Sci USA 88:3213–3217

    PubMed  Google Scholar 

  • Kräusslich H-G, Fäcke M, Heuser A-M et al (1995) The spacer peptide between human immunodeficiency virus capsid and nucleocapsid proteins is essential for ordered assembly and viral infectivity. J Virol 69:3407–3419

    PubMed  Google Scholar 

  • Lanman J, Lam TT, Barnes S et al (2003) Identification of novel interactions in HIV-1 capsid protein assembly by high-resolution mass spectrometry. J Mol Biol 325:759–772

    PubMed  CAS  Google Scholar 

  • Lanman J, Lam TT, Emmett MR et al (2004) Key interactions in HIV-1 maturation identified by hydrogen-deuterium exchange. Nat Struct Mol Biol 11:676–677

    PubMed  CAS  Google Scholar 

  • Lapatto R, Blundell T, Hemmings A et al (1989) X-ray analysis of HIV-1 proteinase at 2.7 Å resolution confirms structural homology among retroviral enzymes. Nature 342:299–302

    PubMed  CAS  Google Scholar 

  • Lata S, Schoehn G, Jain A et al (2008) Helical structures of ESCRT-III are disassembled by VPS4. Science 321:1354–1357

    PubMed  CAS  Google Scholar 

  • Le Blanc I, Prévost M-C, Dokhélar M-C et al (2002) The PPPY motif of human T-cell leukemia virus type 1 Gag protein is required early in the budding process. J Virol 76:10024–10029

    PubMed  Google Scholar 

  • Li S, Hill CP, Sundquist WI et al (2000) Image reconstructions of helical assemblies of the HIV-1 CA protein. Nature 407:409–413

    PubMed  CAS  Google Scholar 

  • Li F, Goila-Gaur R, Salzwedel K et al (2003) PA-457: a potent HIV inhibitor that disrupts core condensation by targeting a late step in Gag processing. Proc Natl Acad Sci USA 100:13555–13560

    PubMed  CAS  Google Scholar 

  • Li H, Dou J, Ding L et al (2007) Myristoylation is required for human immunodeficiency virus type 1 Gag-Gag multimerization in mammalian cells. J Virol 81:12899–12910

    PubMed  CAS  Google Scholar 

  • Liang C, Hu J, Russell RS et al (2002) Characterization of a putative α-helix across the capsid-SP1 boundary that is critical for the multimerization of human immunodeficiency virus type 1 Gag. J Virol 76:11729–11737

    PubMed  CAS  Google Scholar 

  • Lopez-Vergès S, Camus G, Blot G et al (2006) Tail-interacting protein TIP47 is a connector between Gag and Env and is required for Env incorporation into HIV-1 virions. Proc Natl Acad Sci USA 103:14947–14952

    PubMed  Google Scholar 

  • Martin-Serrano J, Zang T, Bieniasz PD (2001) HIV-1 and Ebola virus encode small peptide motifs that recruit Tsg101 to sites of particle assembly to facilitate egress. Nat Med 7:1313–1319

    PubMed  CAS  Google Scholar 

  • Massiah MA, Starich MR, Paschall C et al (1994) Three-dimensional structure of the human immunodeficiency virus type 1 matrix protein. J Mol Biol 244:198–223

    PubMed  CAS  Google Scholar 

  • Miyazaki Y, Garcia EL, King SR et al (2010) An RNA structural switch regulates diploid genome packaging by Moloney murine leukemia virus. J Mol Biol 396:141–152

    PubMed  CAS  Google Scholar 

  • Monroe EB, Kang S, Kyere SK et al (2010) Hydrogen/deuterium exchange analysis of HIV-1 capsid assembly and maturation. Structure 18:1483–1491

    PubMed  CAS  Google Scholar 

  • Morellet N, Druillennec S, Lenoir C et al (2005) Helical structure determined by NMR of the HIV-1 (345-392) Gag sequence, surrounding p2: implications for particle assembly and RNA packaging. Protein Sci 14:375–386

    PubMed  CAS  Google Scholar 

  • Morita E, Sandrin V, Chung H-Y et al (2007) Human ESCRT and ALIX proteins interact with proteins of the midbody and function in cytokinesis. EMBO J 26:4215–4227

    PubMed  CAS  Google Scholar 

  • Mortuza GB, Haire LF, Stevens A et al (2004) High-resolution structure of a retroviral capsid hexameric amino-terminal domain. Nature 431:481–485

    PubMed  CAS  Google Scholar 

  • Mortuza GB, Dodding MP, Goldstone DC et al (2008) Structure of B-MLV capsid amino-terminal domain reveals key features of viral tropism, Gag assembly and core formation. J Mol Biol 376:1493–1508

    PubMed  CAS  Google Scholar 

  • Mortuza GB, Goldstone DC, Pashley C et al (2009) Structure of the capsid amino-terminal domain from the betaretrovirus, Jaagsiekte sheep retrovirus. J Mol Biol 386:1179–1192

    PubMed  CAS  Google Scholar 

  • Müller B, Anders M, Akiyama H et al (2009) HIV-1 Gag processing intermediates trans-dominantly interfere with HIV-1 infectivity. J Biol Chem 284:29692–29703

    PubMed  Google Scholar 

  • Murakami T, Freed EO (2000a) Genetic evidence for an interaction between human immunodeficiency virus type 1 matrix and α-helix 2 of the gp41 cytoplasmic tail. J Virol 74:3548–3554

    PubMed  CAS  Google Scholar 

  • Murakami T, Freed EO (2000b) The long cytoplasmic tail of gp41 is required in a cell type-dependent manner for HIV-1 envelope glycoprotein incorporation into virions. Proc Natl Acad Sci USA 97:343–348

    PubMed  CAS  Google Scholar 

  • Nandhagopal N, Simpson AA, Johnson MC et al (2004) Dimeric Rous sarcoma virus capsid protein structure relevant to immature Gag assembly. J Mol Biol 335:275–282

    PubMed  CAS  Google Scholar 

  • Navia MA, Fitzgerald PMD, McKeever BM et al (1989) Three-dimensional structure of aspartyl protease from human immunodeficiency virus HIV-1. Nature 337:615–620

    PubMed  CAS  Google Scholar 

  • Newman JL, Butcher EW, Patel DT et al (2004) Flexibility in the P2 domain of the HIV-1 Gag polyprotein. Protein Sci 13:2101–2107

    PubMed  CAS  Google Scholar 

  • Nguyen DH, Hildreth JE (2000) Evidence for budding of human immunodeficiency virus type 1 selectively from glycolipid-enriched membrane lipid rafts. J Virol 74:3264–3272

    PubMed  CAS  Google Scholar 

  • Ono A, Freed EO (2001) Plasma membrane rafts play a critical role in HIV-1 assembly and release. Proc Natl Acad Sci USA 98:13925–13930

    PubMed  CAS  Google Scholar 

  • Ono A, Demirov D, Freed EO (2000) Relationship between human immunodeficiency virus type 1 Gag multimerization and membrane binding. J Virol 74:5142–5150

    PubMed  CAS  Google Scholar 

  • Ono A, Ablan SD, Lockett SJ et al (2004) Phosphatidylinositol (4,5) bisphosphate regulates HIV-1 Gag targeting to the plasma membrane. Proc Natl Acad Sci USA 101:14889–14894

    PubMed  CAS  Google Scholar 

  • Paillart J-C, Göttlinger HG (1999) Opposing effects of human immunodeficiency virus type 1 matrix mutations support a myristyl switch model of Gag membrane targeting. J Virol 73:2604–2612

    PubMed  CAS  Google Scholar 

  • Pettit SC, Sheng N, Tritch R et al (1998) The regulation of sequential processing of HIV-1 Gag by the viral protease. Adv Exp Med Biol 436:15–25

    PubMed  CAS  Google Scholar 

  • Phillips JM, Murray PS, Murray D et al (2008) A molecular switch required for retrovirus assembly participates in the hexagonal immature lattice. EMBO J 27:1411–1420

    PubMed  CAS  Google Scholar 

  • Pornillos O, Alam SL, Davis DR et al (2002) Structure of the Tsg101 UEV domain in complex with the PTAP motif of the HIV-1 p6 protein. Nat Struct Biol 9:812–817

    PubMed  CAS  Google Scholar 

  • Pornillos O, Ganser-Pornillos BK, Kelly BN et al (2009) X-ray structures of the hexameric building block of the HIV capsid. Cell 137:1282–1292

    PubMed  Google Scholar 

  • Pornillos O, Ganser-Pornillos BK, Banumathi S et al (2010) Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. J Mol Biol 401:985–995

    PubMed  CAS  Google Scholar 

  • Pornillos O, Ganser-Pornillos BK, Yeager M (2011) Atomic-level modelling of the HIV capsid. Nature 469:424–427

    PubMed  CAS  Google Scholar 

  • Purdy JG, Flanagan JM, Ropson IJ et al (2008) Critical role of conserved hydrophobic residues within the major homology region in mature retroviral capsid assembly. J Virol 82:5951–5961

    PubMed  CAS  Google Scholar 

  • Purdy JG, Flanagan JM, Ropson IJ et al (2009) Retroviral capsid assembly: a role for the CA dimer in initiation. J Mol Biol 389:438–451

    PubMed  CAS  Google Scholar 

  • Reil H, Bukovsky AA, Gelderblom HR et al (1998) Efficient HIV-1 replication can occur in the absence of the viral matrix protein. EMBO J 17:2699–2708

    PubMed  CAS  Google Scholar 

  • Rumlova-Klikova M, Hunter E, Nermut MV et al (2000) Analysis of Mason-Pfizer monkey virus Gag domains required for capsid assembly in bacteria: role of the N-terminal proline residue of CA in directing particle shape. J Virol 74:8452–8459

    PubMed  CAS  Google Scholar 

  • Saad JS, Miller J, Tai J et al (2006) Structural basis for targeting HIV-1 Gag proteins to the plasma membrane for virus assembly. Proc Natl Acad Sci USA 103:11364–11369

    PubMed  CAS  Google Scholar 

  • Spearman P, Wang J-J, Heyden NV et al (1994) Identification of human immunodeficiency virus type 1 Gag protein domains essential to membrane binding and particle assembly. J Virol 68:3232–3242

    PubMed  CAS  Google Scholar 

  • Spearman P, Horton R, Ratner L et al (1997) Membrane binding of human immunodeficiency virus type 1 matrix protein in vivo supports a conformational myristyl switch mechanism. J Virol 71:6582–6592

    PubMed  CAS  Google Scholar 

  • Strack B, Calistri A, Craig S et al (2003) AIP1/ALIX is a binding partner for HIV-1 p6 and EIAV p9 functioning in virus budding. Cell 114:689–699

    PubMed  CAS  Google Scholar 

  • Swanstrom R, Wills JW (1997) Synthesis, assembly and processing of viral proteins. In: Coffin JM, Hughes SH, Varmus HE (eds) Retroviruses. Cold Spring Harbor Laboratory Press, New York

    Google Scholar 

  • Tang C, Ndassa Y, Summers MF (2002) Structure of the N-terminal 283-residue fragment of the immature HIV-1 Gag polyprotein. Nat Struct Biol 9:537–543

    PubMed  CAS  Google Scholar 

  • Tang C, Loeliger E, Luncsford P et al (2004) Entropic switch regulates myristate exposure in the HIV-1 matrix protein. Proc Natl Acad Sci USA 101:517–522

    PubMed  CAS  Google Scholar 

  • Ternois F, Sticht J, Duquerroy S et al (2005) The HIV-1 capsid protein C-terminal domain in complex with a virus assembly inhibitor. Nat Struct Mol Biol 12:678–682

    PubMed  CAS  Google Scholar 

  • Tritch RJ, Cheng Y-SE, Yin FH et al (1991) Mutagenesis of protease cleavage sites in the human immunodeficiency virus type 1 Gag polyprotein. J Virol 65:922–930

    PubMed  CAS  Google Scholar 

  • Usami Y, Popov S, Popova E et al (2008) Efficient and specific rescue of human immunodeficiency virus type 1 budding defects by a Nedd4-like ubiquitin ligase. J Virol 82:4898–4907

    PubMed  CAS  Google Scholar 

  • VerPlank L, Bouamr F, LaGrassa TJ et al (2001) Tsg101, a homologue of ubiquitin-conjugating (E2) enzymes, binds the L domain in HIV type 1 Pr55Gag. Proc Natl Acad Sci USA 98:7724–7729

    PubMed  CAS  Google Scholar 

  • Vogt VM (1997) Retroviral virions and genomes. In: Coffin JM, Hughes SH, Varmus HE (eds) Retroviruses. Cold Spring Harbor Laboratory Press, New York

    Google Scholar 

  • von Schwedler UK, Stemmler TL, Klishko VY et al (1998) Proteolytic refolding of the HIV-1 capsid protein amino-terminus facilitates viral core assembly. EMBO J 17:1555–1568

    Google Scholar 

  • von Schwedler UK, Stray KM, Garrus JE et al (2003a) Functional surfaces of the human immunodeficiency virus type 1 capsid protein. J Virol 77:5439–5450

    Google Scholar 

  • von Schwedler UK, Stuchell M, Müller B et al (2003b) The protein network of HIV budding. Cell 114:701–713

    Google Scholar 

  • Wang C-T, Zhang Y, McDermott J et al (1993) Conditional infectivity of a human immunodeficiency virus matrix domain deletion mutant. J Virol 67:7067–7076

    PubMed  CAS  Google Scholar 

  • Wang MQ, Kim W, Gao G et al (2003) Endophilins interact with Moloney murine leukemia virus Gag and modulate virion production. J Biol 3:4

    PubMed  Google Scholar 

  • Watts JM, Dang KK, Gorelick RJ et al (2009) Architecture and secondary structure of an entire HIV-1 RNA genome. Nature 460:711–716

    PubMed  CAS  Google Scholar 

  • Wiegers K, Rutter G, Kottler H et al (1998) Sequential steps in human immunodeficiency virus particle maturation revealed by alterations of individual Gag polyprotein cleavage sites. J Virol 72:2846–2854

    PubMed  CAS  Google Scholar 

  • Wollert T, Wunder C, Lippincott-Schwartz J et al (2009) Membrane scission by the ESCRT-III complex. Nature 458:172–177

    PubMed  CAS  Google Scholar 

  • Wong HC, Shin R, Krishna NR (2008) Solution structure of a double mutant of the carboxy-terminal dimerization domain of the HIV-1 capsid protein. Biochemistry 47:2289–2297

    PubMed  CAS  Google Scholar 

  • Worthylake DK, Wang H, Yoo S et al (1999) Structures of the HIV-1 capsid protein dimerization domain at 2.6 Å resolution. Acta Crystallogr D Biol Crystallogr 55:85–92

    PubMed  CAS  Google Scholar 

  • Wright ER, Schooler JB, Ding HJ et al (2007) Electron cryotomography of immature HIV-1 virions reveals the structure of the CA and SP1 Gag shells. EMBO J 26:2218–2226

    PubMed  CAS  Google Scholar 

  • Yasuda J, Hunter E, Nakao M et al (2002) Functional involvement of a novel Nedd4-like ubiquitin ligase on retrovirus budding. EMBO Rep 3:636–640

    PubMed  CAS  Google Scholar 

  • Yeager M, Wilson-Kubalek EM, Weiner SG et al (1998) Supramolecular organization of immature and mature murine leukemia virus revealed by electron cryo-microscopy: implications for retroviral assembly mechanisms. Proc Natl Acad Sci USA 95:7299–7304

    PubMed  CAS  Google Scholar 

  • Yu X, Yuan X, Matsuda Z et al (1992) The matrix protein of human immunodeficiency virus type 1 is required for incorporation of viral envelope protein into mature virions. J Virol 66:4966–4971

    PubMed  CAS  Google Scholar 

  • Zacharias DA, Violin JD, Newton AC et al (2002) Partitioning of lipid-modified monomeric GFPs into membrane microdomains of live cells. Science 296:913–916

    PubMed  CAS  Google Scholar 

  • Zhai Q, Fisher RD, Chung H-Y et al (2008) Structural and functional studies of ALIX interactions with YPX n L late domains of HIV-1 and EIAV. Nat Struct Mol Biol 15:43–49

    PubMed  CAS  Google Scholar 

  • Zhang Y, Barklis E (1997) Effects of nucleocapsid mutations on human immunodeficiency virus assembly and RNA encapsidation. J Virol 71:6765–6776

    PubMed  CAS  Google Scholar 

  • Zhang W, Mukhopadhyay S, Pletnev SV et al (2002) Placement of the structural proteins in Sindbis virus. J Virol 76:11645–11658

    PubMed  CAS  Google Scholar 

  • Zhou W, Parent LJ, Wills JW et al (1994) Identification of a membrane-binding domain within the amino-terminal region of human immunodeficiency virus type 1 Gag protein which interacts with acidic phospholipids. J Virol 68:2556–2569

    PubMed  CAS  Google Scholar 

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Acknowledgments

HIV research in the Yeager laboratory is supported by grants from the US National Institutes of Health (RO1-GM066087 and P50-GM082545). We thank John Briggs, Rebecca Craven, Alasdair Steven, and Elizabeth Wright for generously supplying materials for figures; Kelly Dryden and Jeong-Hyun Lee for assistance in preparing figures; and Wes Sundquist for helpful discussions. We apologize to colleagues whose works were not cited due to lack of space or inadvertent omission.

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  1. Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, 800736, Charlottesville, VA, 22908, USA

    Barbie K. Ganser-Pornillos, Mark Yeager & Owen Pornillos

  2. Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Barbie K. Ganser-Pornillos, Mark Yeager & Owen Pornillos

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  1. Barbie K. Ganser-Pornillos
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  2. Mark Yeager
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  3. Owen Pornillos
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Correspondence to Barbie K. Ganser-Pornillos , Mark Yeager or Owen Pornillos .

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  1. Dept. Biological Sciences, Purdue University, W. State St. 915, West Lafayette, 47907-2054, Indiana, USA

    Michael G. Rossmann

  2. Dept. Biology, Catholic University of America, Washington, 20064, District of Columbia, USA

    Venigalla B. Rao

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Ganser-Pornillos, B.K., Yeager, M., Pornillos, O. (2012). Assembly and Architecture of HIV. In: Rossmann, M., Rao, V. (eds) Viral Molecular Machines. Advances in Experimental Medicine and Biology, vol 726. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-0980-9_20

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