1932

Abstract

Assembly, part of the late stages of the retroviral life cycle, begins when the structural polyprotein Gag associates with viral genomic RNA. Ultimately, more than a thousand Gag molecules form a spherical immature virion. Maturation takes place soon after or concomitantly with virus budding and is initiated as Gag is cleaved by the retroviral protease into its constituent protein domains. The immature core is thought to disassemble and the liberated CA proteins to reassemble into a morphologically distinct mature capsid. In vitro assembly with derivatives of Gag and CA has been used to study retroviruses for over two decades. In this review, we examine the discovery and development of three major model systems [human immunodeficiency virus type 1 (HIV-1), Rous sarcoma virus (RSV), and Mason–Pfizer monkey virus (MPMV)] and discuss structural features and aspects of the retroviral assembly pathway that have been uncovered using in vitro assembly. We also put forward two major unresolved questions in the field and propose future avenues of research.

Keyword(s): CAcapsidGagHIV-1MPMVRSV
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2014-09-29
2024-06-06
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Literature Cited

  1. Fuller SD, Wilk T, Gowen BE, Krausslich HG, Vogt VM. 1.  1997. Cryo–electron microscopy reveals ordered domains in the immature HIV-1 particle. Curr. Biol. 7:729–38 [Google Scholar]
  2. Yeager M, Wilson-Kubalek EM, Weiner SG, Brown PO, Rein A. 2.  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 95:7299–304 [Google Scholar]
  3. Wright ER, Schooler JB, Ding HJ, Kieffer C, Fillmore C. 3.  et al. 2007. Electron cryotomography of immature HIV-1 virions reveals the structure of the CA and SP1 Gag shells. EMBO J. 26:2218–26 [Google Scholar]
  4. Bharat TA, Davey NE, Ulbrich P, Riches JD, de Marco A. 4.  et al. 2012. Structure of the immature retroviral capsid at 8 Å resolution by cryo–electron microscopy. Nature 487:385–89First higher-resolution structure of the immature retroviral lattice solved (at ∼8 Å) using MPMV tubes. [Google Scholar]
  5. Briggs JA, Riches JD, Glass B, Bartonova V, Zanetti G, Krausslich HG. 5.  2009. Structure and assembly of immature HIV. Proc. Natl. Acad. Sci. USA 106:11090–95 [Google Scholar]
  6. de Marco A, Davey NE, Ulbrich P, Phillips JM, Lux V. 6.  et al. 2010. Conserved and variable features of Gag structure and arrangement in immature retrovirus particles. J. Virol. 84:11729–36 [Google Scholar]
  7. Briggs JA, Simon MN, Gross I, Krausslich HG, Fuller SD. 7.  et al. 2004. The stoichiometry of Gag protein in HIV-1. Nat. Struct. Mol. Biol. 11:672–75 [Google Scholar]
  8. Benjamin J, Ganser-Pornillos BK, Tivol WF, Sundquist WI, Jensen GJ. 8.  2005. Three-dimensional structure of HIV-1 virus-like particles by electron cryotomography. J. Mol. Biol. 346:577–88 [Google Scholar]
  9. Keller PW, Huang RK, England MR, Waki K, Cheng N. 9.  et al. 2013. A two-pronged structural analysis of retroviral maturation indicates that core formation proceeds by a disassembly-reassembly pathway rather than a displacive transition. J. Virol. 87:13655–64 [Google Scholar]
  10. Ganser-Pornillos BK, von Schwedler UK, Stray KM, Aiken C, Sundquist WI. 10.  2004. Assembly properties of the human immunodeficiency virus type 1 CA protein. J. Virol. 78:2545–52 [Google Scholar]
  11. Butan C, Winkler DC, Heymann JB, Craven RC, Steven AC. 11.  2008. RSV capsid polymorphism correlates with polymerization efficiency and envelope glycoprotein content: implications that nucleation controls morphogenesis. J. Mol. Biol. 376:1168–81 [Google Scholar]
  12. de Marco A, Muller B, Glass B, Riches JD, Krausslich HG, Briggs JA. 12.  2010. Structural analysis of HIV-1 maturation using cryo–electron tomography. PLoS Pathog. 6:e1001215 [Google Scholar]
  13. Wiegers K, Rutter G, Kottler H, Tessmer U, Hohenberg H, Krausslich HG. 13.  1998. Sequential steps in human immunodeficiency virus particle maturation revealed by alterations of individual Gag polyprotein cleavage sites. J. Virol. 72:2846–54 [Google Scholar]
  14. Campbell S, Vogt VM. 14.  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. 71:4425–35 [Google Scholar]
  15. Campbell S, Fisher RJ, Towler EM, Fox S, Issaq HJ. 15.  et al. 2001. Modulation of HIV-like particle assembly in vitro by inositol phosphates. Proc. Natl. Acad. Sci. USA 98:10875–79First evidence that retroviral assembly may be controlled through conformational changes at the monomeric level. [Google Scholar]
  16. Ehrlich LS, Agresta BE, Carter CA. 16.  1992. Assembly of recombinant human immunodeficiency virus type 1 capsid protein in vitro. J. Virol. 66:4874–83 [Google Scholar]
  17. Gross I, Hohenberg H, Krausslich HG. 17.  1997. In vitro assembly properties of purified bacterially expressed capsid proteins of human immunodeficiency virus. Eur. J. Biochem. 249:592–600 [Google Scholar]
  18. Klikova M, Rhee SS, Hunter E, Ruml T. 18.  1995. Efficient in vivo and in vitro assembly of retroviral capsids from Gag precursor proteins expressed in bacteria. J. Virol. 69:1093–98First immature in vitro assembly system using MPMV Gag. [Google Scholar]
  19. Campbell S, Vogt VM. 19.  1995. Self-assembly in vitro of purified CA-NC proteins from Rous sarcoma virus and human immunodeficiency virus type 1. J. Virol. 69:6487–97 [Google Scholar]
  20. Affranchino JL, Gonzalez SA. 20.  2010. In vitro assembly of the feline immunodeficiency virus Gag polyprotein. Virus Res. 150:153–57 [Google Scholar]
  21. Datta SA, Zuo X, Clark PK, Campbell SJ, Wang YX, Rein A. 21.  2011. Solution properties of murine leukemia virus Gag protein: differences from HIV-1 Gag. J. Virol. 85:12733–41 [Google Scholar]
  22. Yu F, Joshi SM, Ma YM, Kingston RL, Simon MN, Vogt VM. 22.  2001. Characterization of Rous sarcoma virus Gag particles assembled in vitro. J. Virol. 75:2753–64 [Google Scholar]
  23. Ganser BK, Li S, Klishko VY, Finch JT, Sundquist WI. 23.  1999. Assembly and analysis of conical models for the HIV-1 core. Science 283:80–83Theory of and evidence for the fullerene cone hypothesis of retroviral capsid assembly. [Google Scholar]
  24. Zhao G, Perilla JR, Yufenyuy EL, Meng X, Chen B. 24.  et al. 2013. Mature HIV-1 capsid structure by cryo–electron microscopy and all-atom molecular dynamics. Nature 497:643–46 [Google Scholar]
  25. Li S, Hill CP, Sundquist WI, Finch JT. 25.  2000. Image reconstructions of helical assemblies of the HIV-1 CA protein. Nature 407:409–13 [Google Scholar]
  26. Butan C, Lokhandwala PM, Purdy JG, Cardone G, Craven RC, Steven AC. 26.  2010. Suppression of a morphogenic mutant in Rous sarcoma virus capsid protein by a second-site mutation: a cryoelectron tomography study. J. Virol. 84:6377–86 [Google Scholar]
  27. Lanman J, Sexton J, Sakalian M, Prevelige PE Jr. 27.  2002. Kinetic analysis of the role of intersubunit interactions in human immunodeficiency virus type 1 capsid protein assembly in vitro. J. Virol. 76:6900–8 [Google Scholar]
  28. Gross I, Hohenberg H, Huckhagel C, Krausslich HG. 28.  1998. N-terminal extension of human immunodeficiency virus capsid protein converts the in vitro assembly phenotype from tubular to spherical particles. J. Virol. 72:4798–810 [Google Scholar]
  29. Campbell S, Rein A. 29.  1999. In vitro assembly properties of human immunodeficiency virus type 1 Gag protein lacking the p6 domain. J. Virol. 73:2270–79 [Google Scholar]
  30. Datta SA, Curtis JE, Ratcliff W, Clark PK, Crist RM. 30.  et al. 2007. Conformation of the HIV-1 Gag protein in solution. J. Mol. Biol. 365:812–24 [Google Scholar]
  31. Gross I, Hohenberg H, Wilk T, Wiegers K, Grattinger M. 31.  et al. 2000. A conformational switch controlling HIV-1 morphogenesis. EMBO J. 19:103–13 [Google Scholar]
  32. Menendez-Arias L, Risco C, Pinto da Silva P, Oroszlan S. 32.  1992. Purification of immature cores of mouse mammary tumor virus and immunolocalization of protein domains. J. Virol. 66:5615–20 [Google Scholar]
  33. Rumlova-Klikova M, Hunter E, Nermut MV, Pichova I, Ruml T. 33.  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. 74:8452–59 [Google Scholar]
  34. Ulbrich P, Haubova S, Nermut MV, Hunter E, Rumlova M, Ruml T. 34.  2006. Distinct roles for nucleic acid in in vitro assembly of purified Mason–Pfizer monkey virus CANC proteins. J. Virol. 80:7089–99 [Google Scholar]
  35. Phillips JM, Murray PS, Murray D, Vogt VM. 35.  2008. A molecular switch required for retrovirus assembly participates in the hexagonal immature lattice. EMBO J. 27:1411–20Biochemical evidence for the Gag hexamer and a structural role for the N-terminal molecular switch. [Google Scholar]
  36. Ma YM, Vogt VM. 36.  2002. Rous sarcoma virus Gag protein–oligonucleotide interaction suggests a critical role for protein dimer formation in assembly. J. Virol. 76:5452–62 [Google Scholar]
  37. Ma YM, Vogt VM. 37.  2004. Nucleic acid binding–induced Gag dimerization in the assembly of Rous sarcoma virus particles in vitro. J. Virol. 78:52–60Nucleic acid acts as a scaffold for Gag dimers, which are assembly capable without further scaffolding. [Google Scholar]
  38. Purdy JG, Flanagan JM, Ropson IJ, Rennoll-Bankert KE, Craven RC. 38.  2008. Critical role of conserved hydrophobic residues within the major homology region in mature retroviral capsid assembly. J. Virol. 82:5951–61Characterized the nucleating role played by CA dimers in the mature assembly pathway. [Google Scholar]
  39. Bailey GD, Hyun JK, Mitra AK, Kingston RL. 39.  2009. Proton-linked dimerization of a retroviral capsid protein initiates capsid assembly. Structure 17:737–48 [Google Scholar]
  40. Purdy JG, Flanagan JM, Ropson IJ, Craven RC. 40.  2009. Retroviral capsid assembly: a role for the CA dimer in initiation. J. Mol. Biol. 389:438–51 [Google Scholar]
  41. Cardone G, Purdy JG, Cheng N, Craven RC, Steven AC. 41.  2009. Visualization of a missing link in retrovirus capsid assembly. Nature 457:694–98Visual evidence of CA pentamers using cryo-EM reconstructions of icosahedral RSV CA particles. [Google Scholar]
  42. Ganser BK, Cheng A, Sundquist WI, Yeager M. 42.  2003. Three-dimensional structure of the M-MuLV CA protein on a lipid monolayer: a general model for retroviral capsid assembly. EMBO J. 22:2886–92 [Google Scholar]
  43. Mayo K, McDermott J, Barklis E. 43.  2002. Hexagonal organization of Moloney murine leukemia virus capsid proteins. Virology 298:30–38 [Google Scholar]
  44. Pornillos O, Ganser-Pornillos BK, Yeager M. 44.  2011. Atomic-level modelling of the HIV capsid. Nature 469:424–27 [Google Scholar]
  45. Briggs JA, Wilk T, Welker R, Krausslich HG, Fuller SD. 45.  2003. Structural organization of authentic, mature HIV-1 virions and cores. EMBO J. 22:1707–15 [Google Scholar]
  46. Gamble TR, Vajdos FF, Yoo S, Worthylake DK, Houseweart M. 46.  et al. 1996. Crystal structure of human cyclophilin A bound to the amino-terminal domain of HIV-1 capsid. Cell 87:1285–94 [Google Scholar]
  47. Gitti RK, Lee BM, Walker J, Summers MF, Yoo S, Sundquist WI. 47.  1996. Structure of the amino-terminal core domain of the HIV-1 capsid protein. Science 273:231–35 [Google Scholar]
  48. Momany C, Kovari LC, Prongay AJ, Keller W, Gitti RK. 48.  et al. 1996. Crystal structure of dimeric HIV-1 capsid protein. Nat. Struct. Biol. 3:763–70 [Google Scholar]
  49. Gamble TR, Yoo S, Vajdos FF, von Schwedler UK, Worthylake DK. 49.  et al. 1997. Structure of the carboxyl-terminal dimerization domain of the HIV-1 capsid protein. Science 278:849–53 [Google Scholar]
  50. Worthylake DK, Wang H, Yoo S, Sundquist WI, Hill CP. 50.  1999. Structures of the HIV-1 capsid protein dimerization domain at 2.6 Å resolution. Acta Crystallogr. D 55:85–92 [Google Scholar]
  51. Kingston RL, Fitzon-Ostendorp T, Eisenmesser EZ, Schatz GW, Vogt VM. 51.  et al. 2000. Structure and self-association of the Rous sarcoma virus capsid protein. Structure 8:617–28 [Google Scholar]
  52. Mortuza GB, Haire LF, Stevens A, Smerdon SJ, Stoye JP, Taylor IA. 52.  2004. High-resolution structure of a retroviral capsid hexameric amino-terminal domain. Nature 431:481–85 [Google Scholar]
  53. Mortuza GB, Dodding MP, Goldstone DC, Haire LF, Stoye JP, Taylor IA. 53.  2008. Structure of B-MLV capsid amino-terminal domain reveals key features of viral tropism, Gag assembly and core formation. J. Mol. Biol. 376:1493–508 [Google Scholar]
  54. Mortuza GB, Goldstone DC, Pashley C, Haire LF, Palmarini M. 54.  et al. 2009. Structure of the capsid amino-terminal domain from the betaretrovirus, Jaagsiekte sheep retrovirus. J. Mol. Biol. 386:1179–92 [Google Scholar]
  55. Nandhagopal N, Simpson AA, Johnson MC, Francisco AB, Schatz GW. 55.  et al. 2004. Dimeric Rous sarcoma virus capsid protein structure relevant to immature Gag assembly. J. Mol. Biol. 335:275–82 [Google Scholar]
  56. Ganser-Pornillos BK, Cheng A, Yeager M. 56.  2007. Structure of full-length HIV-1 CA: a model for the mature capsid lattice. Cell 131:70–79 [Google Scholar]
  57. Campos-Olivas R, Newman JL, Summers MF. 57.  2000. Solution structure and dynamics of the Rous sarcoma virus capsid protein and comparison with capsid proteins of other retroviruses. J. Mol. Biol. 296:633–49 [Google Scholar]
  58. Macek P, Chmelik J, Krizova I, Kaderavek P, Padrta P. 58.  et al. 2009. NMR structure of the N-terminal domain of capsid protein from the Mason–Pfizer monkey virus. J. Mol. Biol. 392:100–14 [Google Scholar]
  59. Lanman J, Lam TT, Barnes S, Sakalian M, Emmett MR. 59.  et al. 2003. Identification of novel interactions in HIV-1 capsid protein assembly by high-resolution mass spectrometry. J. Mol. Biol. 325:759–72 [Google Scholar]
  60. von Schwedler UK, Stray KM, Garrus JE, Sundquist WI. 60.  2003. Functional surfaces of the human immunodeficiency virus type 1 capsid protein. J. Virol. 77:5439–50 [Google Scholar]
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