Cellular Trafficking Mechanisms in the Assembly and Release of HIV

  • Sebastian Giese
  • Mark Marsh


All enveloped viruses depend on cellular membranes for key aspects of their replication cycles. This is no less true for human immunodeficiency viruses (HIV types 1 and 2 [HIV-1 and HIV-2]) and the related simian immunodeficiency viruses (SIV), and in particular for the events in the virus life cycle when the components of infectious virions are brought together, in the context of a cellular membrane system, to form new virus particles. The fidelity of this process is crucial: Failure of the virus to couple to key cellular trafficking pathways can compromise the infectivity of new virus particles and, in simian models at least, can have a marked impact on pathogenesis. Moreover, viruses modulate the trafficking of cellular components that would otherwise inhibit the release of assembled particles. Here we discuss current views of the mechanisms through which HIV-1 and its close relatives interact with cellular trafficking systems to mediate the assembly and release of infectious virus particles.


Human Immunodeficiency Virus Lipid Raft Simian Immunodeficiency Virus Virus Assembly Human Immunodeficiency Virus Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Large hydrophobic amino acid


Adaptor protein


Capsid protein


Detergent-resistant membrane


Electron microscopy


Envelope protein


Endoplasmic reticulum


Endosomal sorting complex required for transport


Fluorescent protein




Human immunodeficiency virus


Intralumenal vesicle




Intracellular plasma membrane-connected compartment




Matrix protein


Monocyte-derived macrophage


Microtubule organising centre


Multivesicular body


Nucleocapsid protein


Nuclear magnetic resonance





PI 5-phosphatase

Phosphatidylinositol 5-phosphatase


Plasma membrane




Reverse transcriptase


Simian immunodeficiency virus


Surface unit


Trans-Golgi network


Total internal reflection fluorescence




Virus-containing compartment



We thank our colleagues in the Medical Research Council Laboratory for Molecular Cell Biology for their ongoing support and discussions; In particular Annegret Pelchen-Matthews, Joe Grove and David Nkwe for critical comments on the manuscript and Rahel Byland for contributing Fig. 4. The Boehringer Ingelheim Fonds provided support for SG. MM is supported by core funding to the MRC Cell Biology Unit.


  1. 1.
    Carlson L-A, Briggs JAG, Glass B, Riches JD, Simon MN, Johnson MC et al (2008) Three-dimensional analysis of budding sites and released virus suggests a revised model for HIV-1 morphogenesis. Cell Host Microbe 4(6):592–599PubMedGoogle Scholar
  2. 2.
    Sundquist WI, Kräusslich H-G (2012) HIV-1 assembly, budding, and maturation. Cold Spring Harb Perspect Med 2(7):a006924Google Scholar
  3. 3.
    Cantin R, Méthot S, Tremblay MJ (2005) Plunder and stowaways: incorporation of cellular proteins by enveloped viruses. J Virol 79(11):6577–6587PubMedGoogle Scholar
  4. 4.
    Chertova E, Chertov O, Coren LV, Roser JD, Trubey CM, Bess JW et al (2006) Proteomic and biochemical analysis of purified human immunodeficiency virus type 1 produced from infected monocyte-derived macrophages. J Virol 80(18):9039–9052PubMedGoogle Scholar
  5. 5.
    Carlton JG, Martin-Serrano J (2007) Parallels between cytokinesis and retroviral budding: a role for the ESCRT machinery. Science 316(5833):1908–1912PubMedGoogle Scholar
  6. 6.
    Katzmann DJ, Babst M, Emr SD (2001) Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I. Cell 106(2):145–155PubMedGoogle Scholar
  7. 7.
    Hislop JN, von Zastrow M (2011) Role of ubiquitination in endocytic trafficking of G-protein-coupled receptors. Traffic 12(2):137–148PubMedGoogle Scholar
  8. 8.
    Elia N, Sougrat R, Spurlin TA, Hurley JH, Lippincott-Schwartz J (2011) Dynamics of endosomal sorting complex required for transport (ESCRT) machinery during cytokinesis and its role in abscission. Proc Natl Acad Sci USA 108(12):4846–4851PubMedGoogle Scholar
  9. 9.
    Wollert T, Wunder C, Lippincott-Schwartz J, Hurley JH (2009) Membrane scission by the ESCRT-III complex. Nature 458(7235):172–177PubMedGoogle Scholar
  10. 10.
    Garrus JE, von Schwedler UK, Pornillos OW, Morham SG, Zavitz KH, Wang HE et al (2001) Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding. Cell 107(1):55–65PubMedGoogle Scholar
  11. 11.
    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(12):1313–1319PubMedGoogle Scholar
  12. 12.
    VerPlank L, Bouamr F, LaGrassa TJ, Agresta B, Kikonyogo A, Leis J et al (2001) Tsg101, a homologue of ubiquitin-conjugating (E2) enzymes, binds the L domain in HIV type 1 Pr55(Gag). Proc Natl Acad Sci USA 98(14):7724–7729PubMedGoogle Scholar
  13. 13.
    Demirov DG, Ono A, Orenstein JM, Freed EO (2002) Overexpression of the N-terminal domain of TSG101 inhibits HIV-1 budding by blocking late domain function. Proc Natl Acad Sci USA 99(2):955–960PubMedGoogle Scholar
  14. 14.
    Ross TM, Oran AE, Cullen BR (1999) Inhibition of HIV-1 progeny virion release by cell-surface CD4 is relieved by expression of the viral Nef protein. Curr Biol 9(12):613–621PubMedGoogle Scholar
  15. 15.
    Neil SJD, Zang T, Bieniasz PD (2008) Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 451(7177):425–430PubMedGoogle Scholar
  16. 16.
    Van Damme N, Goff D, Katsura C, Jorgenson RL, Mitchell R, Johnson MC et al (2008) The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein. Cell Host Microbe 3(4):245–252PubMedGoogle Scholar
  17. 17.
    Kirchhoff F (2010) Immune evasion and counteraction of restriction factors by HIV-1 and other primate lentiviruses. Cell Host Microbe 8(1):55–67PubMedGoogle Scholar
  18. 18.
    Popov S, Strack B, Sanchez-Merino V, Popova E, Rosin H, Göttlinger HG (2011) Human immunodeficiency virus type 1 and related primate lentiviruses engage clathrin through Gag-Pol or Gag. J Virol 85(8):3792–3801PubMedGoogle Scholar
  19. 19.
    Zhang F, Zang T, Wilson SJ, Johnson MC, Bieniasz PD (2011) Clathrin facilitates the morphogenesis of retrovirus particles. PLoS Pathog 7(6):e1002119PubMedGoogle Scholar
  20. 20.
    Jouvenet N, Neil SJD, Bess C, Johnson MC, Virgen CA, Simon SM et al (2006) Plasma membrane is the site of productive HIV-1 particle assembly. PLoS Biol 4(12):e435PubMedGoogle Scholar
  21. 21.
    Finzi A, Orthwein A, Mercier J, Cohen EA (2007) Productive human immunodeficiency virus type 1 assembly takes place at the plasma membrane. J Virol 81(14):7476–7490PubMedGoogle Scholar
  22. 22.
    Ono A, Ablan SD, Lockett SJ, Nagashima K, Freed EO (2004) Phosphatidylinositol (4,5) bisphosphate regulates HIV-1 Gag targeting to the plasma membrane. Proc Natl Acad Sci USA 101(41):14889–14894PubMedGoogle Scholar
  23. 23.
    Saad JS, Miller J, Tai J, Kim A, Ghanam RH, Summers MF (2006) Structural basis for targeting HIV-1 Gag proteins to the plasma membrane for virus assembly. Proc Natl Acad Sci USA 103(30):11364–11369PubMedGoogle Scholar
  24. 24.
    Jouvenet N, Bieniasz PD, Simon SM (2008) Imaging the biogenesis of individual HIV-1 virions in live cells. Nature 454(7201):236–240PubMedGoogle Scholar
  25. 25.
    Ivanchenko S, Godinez WJ, Lampe M, Kräusslich H-G, Eils R, Rohr K et al (2009) Dynamics of HIV-1 assembly and release. PLoS Pathog 5(11):e1000652PubMedGoogle Scholar
  26. 26.
    Raposo G, Moore M, Innes D, Leijendekker R, Leigh-Brown A, Benaroch P et al (2002) Human macrophages accumulate HIV-1 particles in MHC II compartments. Traffic 3(10):718–729PubMedGoogle Scholar
  27. 27.
    Deneka M, Pelchen-Matthews A, Byland R, Ruiz-Mateos E, Marsh M (2007) In macrophages, HIV-1 assembles into an intracellular plasma membrane domain containing the tetraspanins CD81, CD9, and CD53. J Cell Biol 177(2):329–341PubMedGoogle Scholar
  28. 28.
    Welsch S, Keppler OT, Habermann A, Allespach I, Krijnse-Locker J, Kräusslich H-G (2007) HIV-1 buds predominantly at the plasma membrane of primary human macrophages. PLoS Pathog 3(3):e36PubMedGoogle Scholar
  29. 29.
    Pelchen-Matthews A, Kramer B, Marsh M (2003) Infectious HIV-1 assembles in late endosomes in primary macrophages. J Cell Biol 162(3):443–455PubMedGoogle Scholar
  30. 30.
    Jouve M, Sol-Foulon N, Watson S, Schwartz O, Benaroch P (2007) HIV-1 buds and accumulates in “nonacidic” endosomes of macrophages. Cell Host Microbe 2(2):85–95PubMedGoogle Scholar
  31. 31.
    Pelchen-Matthews A, Giese S, Mlcochova P, Turner J, Marsh M (2012) β2 integrin adhesion complexes maintain the integrity of HIV-1 assembly compartments in primary macrophages. Traffic 13(2):273–291PubMedGoogle Scholar
  32. 32.
    Welsch S, Groot F, Kräusslich H-G, Keppler OT, Sattentau QJ (2011) Architecture and regulation of the HIV-1 assembly and holding compartment in macrophages. J Virol 85(15):7922–7927PubMedGoogle Scholar
  33. 33.
    Mellman I, Fuchs R, Helenius A (1986) Acidification of the endocytic and exocytic pathways. Annu Rev Biochem 55:663–700PubMedGoogle Scholar
  34. 34.
    Joshi A, Ablan SD, Soheilian F, Nagashima K, Freed EO (2009) Evidence that productive human immunodeficiency virus type 1 assembly can occur in an intracellular compartment. J Virol 83(11):5375–5387PubMedGoogle Scholar
  35. 35.
    Kohl NE, Emini EA, Schleif WA, Davis LJ, Heimbach JC, Dixon RA et al (1988) Active human immunodeficiency virus protease is required for viral infectivity. Proc Natl Acad Sci USA 85(13):4686–4690PubMedGoogle Scholar
  36. 36.
    Bijlmakers MJ, Marsh M (1999) Trafficking of an acylated cytosolic protein: newly synthesized p56(lck) travels to the plasma membrane via the exocytic pathway. J Cell Biol 145(3):457–468PubMedGoogle Scholar
  37. 37.
    Choy E, Chiu VK, Silletti J, Feoktistov M, Morimoto T, Michaelson D et al (1999) Endomembrane trafficking of ras: the CAAX motif targets proteins to the ER and Golgi. Cell 98(1):69–80PubMedGoogle Scholar
  38. 38.
    Navarro-Lérida I, Alvarez-Barrientos A, Rodríguez-Crespo I (2006) N-terminal palmitoylation within the appropriate amino acid environment conveys on NOS2 the ability to progress along the intracellular sorting pathways. J Cell Sci 119(Pt 8):1558–1569PubMedGoogle Scholar
  39. 39.
    Jäger S, Cimermancic P, Gulbahce N, Johnson JR, McGovern KE, Clarke SC et al (2012) Global landscape of HIV-human protein complexes. Nature 481(7381):365–370Google Scholar
  40. 40.
    Ott DE, Coren LV, Copeland TD, Kane BP, Johnson DG, Sowder RC et al (1998) Ubiquitin is covalently attached to the p6Gag proteins of human immunodeficiency virus type 1 and simian immunodeficiency virus and to the p12Gag protein of Moloney murine leukemia virus. J Virol 72(4):2962–2968PubMedGoogle Scholar
  41. 41.
    Ott DE, Coren LV, Chertova EN, Gagliardi TD, Schubert U (2000) Ubiquitination of HIV-1 and MuLV Gag. Virology 278(1):111–121PubMedGoogle Scholar
  42. 42.
    Gottwein E, Kräusslich H-G (2005) Analysis of human immunodeficiency virus type 1 Gag ubiquitination. J Virol 79(14):9134–9144PubMedGoogle Scholar
  43. 43.
    Schubert U, Antón LC, Gibbs J, Norbury CC, Yewdell JW, Bennink JR (2000) Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature 404(6779):770–774PubMedGoogle Scholar
  44. 44.
    Lingappa JR, Hill RL, Wong ML, Hegde RS (1997) A multistep, ATP-dependent pathway for assembly of human immunodeficiency virus capsids in a cell-free system. J Cell Biol 136(3):567–581PubMedGoogle Scholar
  45. 45.
    Zimmerman C, Klein KC, Kiser PK, Singh AR, Firestein BL, Riba SC et al (2002) Identification of a host protein essential for assembly of immature HIV-1 capsids. Nature 415(6867):88–92PubMedGoogle Scholar
  46. 46.
    Dooher JE, Schneider BL, Reed JC, Lingappa JR (2007) Host ABCE1 is at plasma membrane HIV assembly sites and its dissociation from Gag is linked to subsequent events of virus production. Traffic 8(3):195–211PubMedGoogle Scholar
  47. 47.
    Kutluay SB, Bieniasz PD (2010) Analysis of the initiating events in HIV-1 particle assembly and genome packaging. PLoS Pathog 6(11):e1001200PubMedGoogle Scholar
  48. 48.
    Tang Y, Winkler U, Freed EO, Torrey TA, Kim W, Li H et al (1999) Cellular motor protein KIF-4 associates with retroviral Gag. J Virol 73(12):10508–10513PubMedGoogle Scholar
  49. 49.
    Martinez NW, Xue X, Berro RG, Kreitzer G, Resh MD (2008) Kinesin KIF4 regulates intracellular trafficking and stability of the human immunodeficiency virus type 1 Gag polyprotein. J Virol 82(20):9937–9950PubMedGoogle Scholar
  50. 50.
    Azevedo C, Burton A, Ruiz-Mateos E, Marsh M, Saiardi A (2009) Inositol pyrophosphate mediated pyrophosphorylation of AP3B1 regulates HIV-1 Gag release. Proc Natl Acad Sci USA 106(50):21161–21166PubMedGoogle Scholar
  51. 51.
    Brass AL, Dykxhoorn DM, Benita Y, Yan N, Engelman A, Xavier RJ et al (2008) Identification of host proteins required for HIV infection through a functional genomic screen. Science 319(5865):921–926PubMedGoogle Scholar
  52. 52.
    Gaudin R, Cunha de Alencar B, Jouve M, Bèrre S, Le Bouder E, Schindler M et al (2012) Critical role for the kinesin KIF3A in the HIV life cycle in primary human macrophages. J Cell Biol 199(3):467–479PubMedGoogle Scholar
  53. 53.
    Dong X, Li H, Derdowski A, Ding L, Burnett A, Chen X et al (2005) AP-3 directs the intracellular trafficking of HIV-1 Gag and plays a key role in particle assembly. Cell 120(5):663–674PubMedGoogle Scholar
  54. 54.
    Dell’Angelica EC, Ohno H, Ooi CE, Rabinovich E, Roche KW, Bonifacino JS (1997) AP-3: an adaptor-like protein complex with ubiquitous expression. EMBO J 16(5):917–928PubMedGoogle Scholar
  55. 55.
    Simpson F, Peden AA, Christopoulou L, Robinson MS (1997) Characterization of the adaptor-related protein complex, AP-3. J Cell Biol 137(4):835–845PubMedGoogle Scholar
  56. 56.
    Le Borgne R, Alconada A, Bauer U, Hoflack B (1998) The mammalian AP-3 adaptor-like complex mediates the intracellular transport of lysosomal membrane glycoproteins. J Biol Chem 273(45):29451–29461PubMedGoogle Scholar
  57. 57.
    Dell’Angelica EC, Shotelersuk V, Aguilar RC, Gahl WA, Bonifacino JS (1999) Altered trafficking of lysosomal proteins in Hermansky-Pudlak syndrome due to mutations in the beta 3A subunit of the AP-3 adaptor. Mol Cell 3(1):11–21PubMedGoogle Scholar
  58. 58.
    Rous BA, Reaves BJ, Ihrke G, Briggs JAG, Gray SR, Stephens DJ et al (2002) Role of adaptor complex AP-3 in targeting wild-type and mutated CD63 to lysosomes. Mol Biol Cell 13(3):1071–1082PubMedGoogle Scholar
  59. 59.
    D’Souza-Schorey C, Chavrier P (2006) ARF proteins: roles in membrane traffic and beyond. Nat Rev Mol Cell Biol 7(5):347–358PubMedGoogle Scholar
  60. 60.
    Joshi A, Garg H, Nagashima K, Bonifacino JS, Freed EO (2008) GGA and Arf proteins modulate retrovirus assembly and release. Mol Cell 30(2):227–238PubMedGoogle Scholar
  61. 61.
    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(45):19114–19119PubMedGoogle Scholar
  62. 62.
    Bryant M, Ratner L (1990) Myristoylation-dependent replication and assembly of human immunodeficiency virus 1. Proc Natl Acad Sci USA 87(2):523–527PubMedGoogle Scholar
  63. 63.
    Yuan X, Yu X, Lee TH, Essex M (1993) Mutations in the N-terminal region of human immunodeficiency virus type 1 matrix protein block intracellular transport of the Gag precursor. J Virol 67(11):6387–6394PubMedGoogle Scholar
  64. 64.
    Freed EO, Orenstein JM, Buckler-White AJ, Martin MA (1994) Single amino acid changes in the human immunodeficiency virus type 1 matrix protein block virus particle production. J Virol 68(8):5311–5320PubMedGoogle Scholar
  65. 65.
    Zhou W, Parent LJ, Wills JW, Resh MD (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(4):2556–2569PubMedGoogle Scholar
  66. 66.
    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(18):8670–8679PubMedGoogle Scholar
  67. 67.
    Ono A, Orenstein JM, Freed EO (2000) Role of the Gag matrix domain in targeting human immunodeficiency virus type 1 assembly. J Virol 74(6):2855–2866PubMedGoogle Scholar
  68. 68.
    Tang C, Loeliger E, Luncsford P, Kinde I, Beckett D, Summers MF (2004) Entropic switch regulates myristate exposure in the HIV-1 matrix protein. Proc Natl Acad Sci USA 101(2):517–522PubMedGoogle Scholar
  69. 69.
    Behnia R, Munro S (2005) Organelle identity and the signposts for membrane traffic. Nature 438(7068):597–604PubMedGoogle Scholar
  70. 70.
    Simons K, Gerl MJ (2010) Revitalizing membrane rafts: new tools and insights. Nat Rev Mol Cell Biol 11(10):688–699PubMedGoogle Scholar
  71. 71.
    Chukkapalli V, Hogue IB, Boyko V, Hu W-S, Ono A (2008) Interaction between the human immunodeficiency virus type 1 Gag matrix domain and phosphatidylinositol-(4,5)-bisphosphate is essential for efficient gag membrane binding. J Virol 82(5):2405–2417PubMedGoogle Scholar
  72. 72.
    Brown FD, Rozelle AL, Yin HL, Balla T, Donaldson JG (2001) Phosphatidylinositol 4,5-bisphosphate and Arf6-regulated membrane traffic. J Cell Biol 154(5):1007–1017PubMedGoogle Scholar
  73. 73.
    Nguyen DH, Hildreth JE (2000) Evidence for budding of human immunodeficiency virus type 1 selectively from glycolipid-enriched membrane lipid rafts. J Virol 74(7):3264–3272PubMedGoogle Scholar
  74. 74.
    Ono A, Freed EO (2001) Plasma membrane rafts play a critical role in HIV-1 assembly and release. Proc Natl Acad Sci USA 98(24):13925–13930PubMedGoogle Scholar
  75. 75.
    Lindwasser OW, Resh MD (2002) Myristoylation as a target for inhibiting HIV assembly: unsaturated fatty acids block viral budding. Proc Natl Acad Sci USA 99(20):13037–13042PubMedGoogle Scholar
  76. 76.
    Aloia RC, Jensen FC, Curtain CC, Mobley PW, Gordon LM (1988) Lipid composition and fluidity of the human immunodeficiency virus. Proc Natl Acad Sci USA 85(3):900–904PubMedGoogle Scholar
  77. 77.
    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(11):5181–5185PubMedGoogle Scholar
  78. 78.
    Brügger B, Glass B, Haberkant P, Leibrecht I, Wieland FT, Kräusslich H-G (2006) The HIV lipidome: a raft with an unusual composition. Proc Natl Acad Sci USA 103(8):2641–2646PubMedGoogle Scholar
  79. 79.
    Chan R, Uchil PD, Jin J, Shui G, Ott DE, Mothes W et al (2008) Retroviruses human immunodeficiency virus and murine leukemia virus are enriched in phosphoinositides. J Virol 82(22):11228–11238PubMedGoogle Scholar
  80. 80.
    Lehmann M, Rocha S, Mangeat B, Blanchet F, Uji-I H, Hofkens J et al (2011) Quantitative Multicolor Super-Resolution Microscopy Reveals Tetherin HIV-1 Interaction. PLoS Pathog 7(12):e1002456PubMedGoogle Scholar
  81. 81.
    Nydegger S, Khurana S, Krementsov DN, Foti M, Thali M (2006) Mapping of tetraspanin-enriched microdomains that can function as gateways for HIV-1. J Cell Biol 173(5):795–807PubMedGoogle Scholar
  82. 82.
    Ruiz-Mateos E, Pelchen-Matthews A, Deneka M, Marsh M (2008) CD63 is not required for production of infectious human immunodeficiency virus type 1 in human macrophages. J Virol 82(10):4751–4761PubMedGoogle Scholar
  83. 83.
    Krementsov DN, Rassam P, Margeat E, Roy NH, Schneider-Schaulies J, Milhiet P-E et al (2010) HIV-1 assembly differentially alters dynamics and partitioning of tetraspanins and raft components. Traffic 11(11):1401–1414PubMedGoogle Scholar
  84. 84.
    Hogue IB, Grover JR, Soheilian F, Nagashima K, Ono A (2011) Gag induces the coalescence of clustered lipid rafts and tetraspanin-enriched microdomains at HIV-1 assembly sites on the plasma membrane. J Virol 85(19):9749–9766PubMedGoogle Scholar
  85. 85.
    Briggs JAG, Riches JD, Glass B, Bartonova V, Zanetti G, Kräusslich H-G (2009) Structure and assembly of immature HIV. Proc Natl Acad Sci USA 106(27):11090–11095PubMedGoogle Scholar
  86. 86.
    Wright ER, Schooler JB, Ding HJ, Kieffer C, Fillmore C, Sundquist WI et al (2007) Electron cryotomography of immature HIV-1 virions reveals the structure of the CA and SP1 Gag shells. EMBO J 26(8):2218–2226PubMedGoogle Scholar
  87. 87.
    Bharat TAM, Davey NE, Ulbrich P, Riches JD, de Marco A, Rumlova M et al (2012) Structure of the immature retroviral capsid at 8 Å resolution by cryo-electron microscopy. Nature 487(7407):385–389PubMedGoogle Scholar
  88. 88.
    Clever J, Sassetti C, Parslow TG (1995) RNA secondary structure and binding sites for gag gene products in the 5′ packaging signal of human immunodeficiency virus type 1. J Virol 69(4):2101–2109PubMedGoogle Scholar
  89. 89.
    Skripkin E, Paillart JC, Marquet R, Ehresmann B, Ehresmann C (1994) Identification of the primary site of the human immunodeficiency virus type 1 RNA dimerization in vitro. Proc Natl Acad Sci USA 91(11):4945–4949PubMedGoogle Scholar
  90. 90.
    Muriaux D, Mirro J, Harvin D, Rein A (2001) RNA is a structural element in retrovirus particles. Proc Natl Acad Sci USA 98(9):5246–5251PubMedGoogle Scholar
  91. 91.
    Hockley DJ, Wood RD, Jacobs JP, Garrett AJ (1988) Electron microscopy of human immunodeficiency virus. J Gen Virol 69(Pt 10):2455–2469PubMedGoogle Scholar
  92. 92.
    Carlson L-A, de Marco A, Oberwinkler H, Habermann A, Briggs JAG, Kräusslich H-G et al (2010) Cryo electron tomography of native HIV-1 budding sites. PLoS Pathog 6(11):e1001173PubMedGoogle Scholar
  93. 93.
    Larson DR, Johnson MC, Webb WW, Vogt VM (2005) Visualization of retrovirus budding with correlated light and electron microscopy. Proc Natl Acad Sci USA 102(43):15453–15458PubMedGoogle Scholar
  94. 94.
    Müller B, Daecke J, Fackler OT, Dittmar MT, Zentgraf H, Kräusslich H-G (2004) Construction and characterization of a fluorescently labeled infectious human immunodeficiency virus type 1 derivative. J Virol 78(19):10803–10813PubMedGoogle Scholar
  95. 95.
    Hübner W, Chen P, Del Portillo A, Liu Y, Gordon RE, Chen BK (2007) Sequence of human immunodeficiency virus type 1 (HIV-1) Gag localization and oligomerization monitored with live confocal imaging of a replication-competent, fluorescently tagged HIV-1. J Virol 81(22):12596–12607PubMedGoogle Scholar
  96. 96.
    Perlman M, Resh MD (2006) Identification of an intracellular trafficking and assembly pathway for HIV-1 gag. Traffic 7(6):731–745PubMedGoogle Scholar
  97. 97.
    Jiménez-Baranda S, Gómez-Moutón C, Rojas A, Martínez-Prats L, Mira E, Ana Lacalle R et al (2007) Filamin-A regulates actin-dependent clustering of HIV receptors. Nat Cell Biol 9(7):838–846PubMedGoogle Scholar
  98. 98.
    Yoder A, Yu D, Dong L, Iyer SR, Xu X, Kelly J et al (2008) HIV envelope-CXCR4 signaling activates cofilin to overcome cortical actin restriction in resting CD4 T cells. Cell 134(5):782–792PubMedGoogle Scholar
  99. 99.
    Davis CB, Dikic I, Unutmaz D, Hill CM, Arthos J, Siani MA et al (1997) Signal transduction due to HIV-1 envelope interactions with chemokine receptors CXCR4 or CCR5. J Exp Med 186(10):1793–1798PubMedGoogle Scholar
  100. 100.
    Zhu P, Liu J, Bess J, Chertova E, Lifson JD, Grisé H et al (2006) Distribution and three-dimensional structure of AIDS virus envelope spikes. Nature 441(7095):847–852PubMedGoogle Scholar
  101. 101.
    Yang X, Kurteva S, Lee S, Sodroski J (2005) Stoichiometry of antibody neutralization of human immunodeficiency virus type 1. J Virol 79(6):3500–3508PubMedGoogle Scholar
  102. 102.
    Yang X, Kurteva S, Ren X, Lee S, Sodroski J (2005) Stoichiometry of envelope glycoprotein trimers in the entry of human immunodeficiency virus type 1. J Virol 79(19):12132–12147PubMedGoogle Scholar
  103. 103.
    Sougrat R, Bartesaghi A, Lifson JD, Bennett AE, Bess JW, Zabransky DJ et al (2007) Electron tomography of the contact between T cells and SIV/HIV-1: implications for viral entry. PLoS Pathog 3(5):e63PubMedGoogle Scholar
  104. 104.
    Magnus C, Rusert P, Bonhoeffer S, Trkola A, Regoes RR (2009) Estimating the stoichiometry of human immunodeficiency virus entry. J Virol 83(3):1523–1531PubMedGoogle Scholar
  105. 105.
    Chojnacki J, Staudt T, Glass B, Bingen P, Engelhardt J, Anders M et al (2012) Maturation-dependent HIV-1 surface protein redistribution revealed by fluorescence nanoscopy. Science 338(6106):524–528PubMedGoogle Scholar
  106. 106.
    Checkley MA, Luttge BG, Freed EO (2011) HIV-1 envelope glycoprotein biosynthesis, trafficking, and incorporation. J Mol Biol 410(4):582–608PubMedGoogle Scholar
  107. 107.
    Land A, Zonneveld D, Braakman I (2003) Folding of HIV-1 envelope glycoprotein involves extensive isomerization of disulfide bonds and conformation-dependent leader peptide cleavage. FASEB J 17(9):1058–1067PubMedGoogle Scholar
  108. 108.
    Willey RL, Bonifacino JS, Potts BJ, Martin MA, Klausner RD (1988) Biosynthesis, cleavage, and degradation of the human immunodeficiency virus 1 envelope glycoprotein gp160. Proc Natl Acad Sci USA 85(24):9580–9584PubMedGoogle Scholar
  109. 109.
    Rousso I, Mixon MB, Chen BK, Kim PS (2000) Palmitoylation of the HIV-1 envelope glycoprotein is critical for viral infectivity. Proc Natl Acad Sci USA 97(25):13523–13525PubMedGoogle Scholar
  110. 110.
    Bonifacino JS, Traub LM (2003) Signals for sorting of transmembrane proteins to endosomes and lysosomes. Annu Rev Biochem 72:395–447PubMedGoogle Scholar
  111. 111.
    LaBranche CC, Sauter MM, Haggarty BS, Vance PJ, Romano J, Hart TK et al (1995) A single amino acid change in the cytoplasmic domain of the simian immunodeficiency virus transmembrane molecule increases envelope glycoprotein expression on infected cells. J Virol 69(9):5217–5227PubMedGoogle Scholar
  112. 112.
    Rowell JF, Stanhope PE, Siliciano RF (1995) Endocytosis of endogenously synthesized HIV-1 envelope protein. Mechanism and role in processing for association with class II MHC. J Immunol 155(1):473–488PubMedGoogle Scholar
  113. 113.
    Sauter MM, Pelchen-Matthews A, Bron R, Marsh M, LaBranche CC, Vance PJ et al (1996) An internalization signal in the simian immunodeficiency virus transmembrane protein cytoplasmic domain modulates expression of envelope glycoproteins on the cell surface. J Cell Biol 132(5):795–811PubMedGoogle Scholar
  114. 114.
    Boge M, Wyss S, Bonifacino JS, Thali M (1998) A membrane-proximal tyrosine-based signal mediates internalization of the HIV-1 envelope glycoprotein via interaction with the AP-2 clathrin adaptor. J Biol Chem 273(25):15773–15778PubMedGoogle Scholar
  115. 115.
    Berlioz-Torrent C, Shacklett BL, Erdtmann L, Delamarre L, Bouchaert I, Sonigo P et al (1999) Interactions of the cytoplasmic domains of human and simian retroviral transmembrane proteins with components of the clathrin adaptor complexes modulate intracellular and cell surface expression of envelope glycoproteins. J Virol 73(2):1350–1361PubMedGoogle Scholar
  116. 116.
    Byland R, Vance PJ, Hoxie JA, Marsh M (2007) A conserved dileucine motif mediates clathrin and AP-2-dependent endocytosis of the HIV-1 envelope protein. Mol Biol Cell 18(2):414–425PubMedGoogle Scholar
  117. 117.
    Bowers K, Pelchen-Matthews A, Höning S, Vance PJ, Creary L, Haggarty BS et al (2000) The simian immunodeficiency virus envelope glycoprotein contains multiple signals that regulate its cell surface expression and endocytosis. Traffic 1(8):661–674PubMedGoogle Scholar
  118. 118.
    Ohno H, Aguilar RC, Fournier MC, Hennecke S, Cosson P, Bonifacino JS (1997) Interaction of endocytic signals from the HIV-1 envelope glycoprotein complex with members of the adaptor medium chain family. Virology 238(2):305–315PubMedGoogle Scholar
  119. 119.
    Wyss S, Berlioz-Torrent C, Boge M, Blot G, Höning S, Benarous R et al (2001) The highly conserved C-terminal dileucine motif in the cytosolic domain of the human immunodeficiency virus type 1 envelope glycoprotein is critical for its association with the AP-1 clathrin adaptor [correction of adapter]. J Virol 75(6):2982–2992PubMedGoogle Scholar
  120. 120.
    Kelly BT, McCoy AJ, Späte K, Miller SE, Evans PR, Höning S et al (2008) A structural explanation for the binding of endocytic dileucine motifs by the AP2 complex. Nature 456(7224):976–979PubMedGoogle Scholar
  121. 121.
    Fultz PN, Vance PJ, Endres MJ, Tao B, Dvorin JD, Davis IC et al (2001) In vivo attenuation of simian immunodeficiency virus by disruption of a tyrosine-dependent sorting signal in the envelope glycoprotein cytoplasmic tail. J Virol 75(1):278–291PubMedGoogle Scholar
  122. 122.
    Díaz E, Pfeffer SR (1998) TIP47: a cargo selection device for mannose 6-phosphate receptor trafficking. Cell 93(3):433–443PubMedGoogle Scholar
  123. 123.
    Wolins NE, Rubin B, Brasaemle DL (2001) TIP47 associates with lipid droplets. J Biol Chem 276(7):5101–5108PubMedGoogle Scholar
  124. 124.
    Barbero P, Buell E, Zulley S, Pfeffer SR (2001) TIP47 is not a component of lipid droplets. J Biol Chem 276(26):24348–24351PubMedGoogle Scholar
  125. 125.
    Blot G, Janvier K, Le Panse S, Benarous R, Berlioz-Torrent C (2003) Targeting of the human immunodeficiency virus type 1 envelope to the trans-Golgi network through binding to TIP47 is required for env incorporation into virions and infectivity. J Virol 77(12):6931–6945PubMedGoogle Scholar
  126. 126.
    Owens RJ, Compans RW (1989) Expression of the human immunodeficiency virus envelope glycoprotein is restricted to basolateral surfaces of polarized epithelial cells. J Virol 63(2):978–982PubMedGoogle Scholar
  127. 127.
    Owens RJ, Dubay JW, Hunter E, Compans RW (1991) Human immunodeficiency virus envelope protein determines the site of virus release in polarized epithelial cells. Proc Natl Acad Sci USA 88(9):3987–3991PubMedGoogle Scholar
  128. 128.
    Jolly C, Kashefi K, Hollinshead M, Sattentau QJ (2004) HIV-1 cell to cell transfer across an Env-induced, actin-dependent synapse. J Exp Med 199(2):283–293PubMedGoogle Scholar
  129. 129.
    Miranda LR, Schaefer BC, Kupfer A, Hu Z, Franzusoff A (2002) Cell surface expression of the HIV-1 envelope glycoproteins is directed from intracellular CTLA-4-containing regulated secretory granules. Proc Natl Acad Sci USA 99(12):8031–8036PubMedGoogle Scholar
  130. 130.
    Caillet M, Janvier K, Pelchen-Matthews A, Delcroix-Genête D, Camus G, Marsh M et al (2011) Rab7A is required for efficient production of infectious HIV-1. PLoS Pathog 7(11):e1002347PubMedGoogle Scholar
  131. 131.
    Yuste E, Reeves JD, Doms RW, Desrosiers RC (2004) Modulation of Env content in virions of simian immunodeficiency virus: correlation with cell surface expression and virion infectivity. J Virol 78(13):6775–6785PubMedGoogle Scholar
  132. 132.
    Leung K, Kim J-O, Ganesh L, Kabat J, Schwartz O, Nabel GJ (2008) HIV-1 assembly: viral glycoproteins segregate quantally to lipid rafts that associate individually with HIV-1 capsids and virions. Cell Host Microbe 3(5):285–292PubMedGoogle Scholar
  133. 133.
    Cosson P (1996) Direct interaction between the envelope and matrix proteins of HIV-1. EMBO J 15(21):5783–5788PubMedGoogle Scholar
  134. 134.
    Dubay JW, Roberts SJ, Hahn BH, Hunter E (1992) Truncation of the human immunodeficiency virus type 1 transmembrane glycoprotein cytoplasmic domain blocks virus infectivity. J Virol 66(11):6616–6625PubMedGoogle Scholar
  135. 135.
    Yu X, Yuan X, Matsuda Z, Lee TH, Essex M (1992) The matrix protein of human immunodeficiency virus type 1 is required for incorporation of viral envelope protein into mature virions. J Virol 66(8):4966–4971PubMedGoogle Scholar
  136. 136.
    Dorfman T, Mammano F, Haseltine WA, Göttlinger HG (1994) Role of the matrix protein in the virion association of the human immunodeficiency virus type 1 envelope glycoprotein. J Virol 68(3):1689–1696PubMedGoogle Scholar
  137. 137.
    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(3):1984–1989PubMedGoogle Scholar
  138. 138.
    Murakami T, Freed EO (2000) Genetic evidence for an interaction between human immunodeficiency virus type 1 matrix and alpha-helix 2 of the gp41 cytoplasmic tail. J Virol 74(8):3548–3554PubMedGoogle Scholar
  139. 139.
    Lopez-Vergès S, Camus G, Blot G, Beauvoir R, Benarous R, Berlioz-Torrent C (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(40):14947–14952PubMedGoogle Scholar
  140. 140.
    Bauby H, Lopez-Vergès S, Hoeffel G, Delcroix-Genête D, Janvier K, Mammano F et al (2010) TIP47 is required for the production of infectious HIV-1 particles from primary macrophages. Traffic 11(4):455–467PubMedGoogle Scholar
  141. 141.
    Henne WM, Buchkovich NJ, Emr SD (2011) The ESCRT pathway. Dev Cell 21(1):77–91PubMedGoogle Scholar
  142. 142.
    Wollert T, Hurley JH (2010) Molecular mechanism of multivesicular body biogenesis by ESCRT complexes. Nature 464(7290):864–869PubMedGoogle Scholar
  143. 143.
    Bieniasz PD (2006) Late budding domains and host proteins in enveloped virus release. Virology 344(1):55–63PubMedGoogle Scholar
  144. 144.
    Göttlinger HG, Dorfman T, Sodroski JG, Haseltine WA (1991) Effect of mutations affecting the p6 gag protein on human immunodeficiency virus particle release. Proc Natl Acad Sci USA 88(8):3195–3199PubMedGoogle Scholar
  145. 145.
    Huang M, Orenstein JM, Martin MA, Freed EO (1995) p6Gag is required for particle production from full-length human immunodeficiency virus type 1 molecular clones expressing protease. J Virol 69(11):6810–6818PubMedGoogle Scholar
  146. 146.
    Fisher RD, Chung H-Y, Zhai Q, Robinson H, Sundquist WI, Hill CP (2007) Structural and biochemical studies of ALIX/AIP1 and its role in retrovirus budding. Cell 128(5):841–852PubMedGoogle Scholar
  147. 147.
    Usami Y, Popov S, Göttlinger HG (2007) Potent rescue of human immunodeficiency virus type 1 late domain mutants by ALIX/AIP1 depends on its CHMP4 binding site. J Virol 81(12):6614–6622PubMedGoogle Scholar
  148. 148.
    Martin-Serrano J, Yarovoy A, Perez-Caballero D, Bieniasz PD, Yaravoy A (2003) Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins. Proc Natl Acad Sci USA 100(21):12414–12419PubMedGoogle Scholar
  149. 149.
    Strack B, Calistri A, Craig S, Popova E, Göttlinger HG (2003) AIP1/ALIX is a binding partner for HIV-1 p6 and EIAV p9 functioning in virus budding. Cell 114(6):689–699PubMedGoogle Scholar
  150. 150.
    von Schwedler UK, Stuchell M, Müller B, Ward DM, Chung H-Y, Morita E et al (2003) The protein network of HIV budding. Cell 114(6):701–713Google Scholar
  151. 151.
    Guizetti J, Schermelleh L, Mäntler J, Maar S, Poser I, Leonhardt H et al (2011) Cortical constriction during abscission involves helices of ESCRT-III-dependent filaments. Science 331(6024):1616–1620PubMedGoogle Scholar
  152. 152.
    Landau NR, Warton M, Littman DR (1988) The envelope glycoprotein of the human immunodeficiency virus binds to the immunoglobulin-like domain of CD4. Nature 334(6178):159–162PubMedGoogle Scholar
  153. 153.
    Lenburg ME, Landau NR (1993) Vpu-induced degradation of CD4: requirement for specific amino acid residues in the cytoplasmic domain of CD4. J Virol 67(12):7238–7245PubMedGoogle Scholar
  154. 154.
    Vincent MJ, Raja NU, Jabbar MA (1993) Human immunodeficiency virus type 1 Vpu protein induces degradation of chimeric envelope glycoproteins bearing the cytoplasmic and anchor domains of CD4: role of the cytoplasmic domain in Vpu-induced degradation in the endoplasmic reticulum. J Virol 67(9):5538–5549PubMedGoogle Scholar
  155. 155.
    Willey RL, Buckler-White A, Strebel K (1994) Sequences present in the cytoplasmic domain of CD4 are necessary and sufficient to confer sensitivity to the human immunodeficiency virus type 1 Vpu protein. J Virol 68(2):1207–1212PubMedGoogle Scholar
  156. 156.
    Margottin F, Bour SP, Durand H, Selig L, Benichou S, Richard V et al (1998) A novel human WD protein, h-beta TrCp, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif. Mol Cell 1(4):565–574PubMedGoogle Scholar
  157. 157.
    Butticaz C, Michielin O, Wyniger J, Telenti A, Rothenberger S (2007) Silencing of both beta-TrCP1 and HOS (beta-TrCP2) is required to suppress human immunodeficiency virus type 1 Vpu-mediated CD4 down-modulation. J Virol 81(3):1502–1505PubMedGoogle Scholar
  158. 158.
    Schubert U, Antón LC, Bacík I, Cox JH, Bour S, Bennink JR et al (1998) CD4 glycoprotein degradation induced by human immunodeficiency virus type 1 Vpu protein requires the function of proteasomes and the ubiquitin-conjugating pathway. J Virol 72(3):2280–2288PubMedGoogle Scholar
  159. 159.
    Meusser B, Sommer T (2004) Vpu-mediated degradation of CD4 reconstituted in yeast reveals mechanistic differences to cellular ER-associated protein degradation. Mol Cell 14(2):247–258PubMedGoogle Scholar
  160. 160.
    Aiken C, Konner J, Landau NR, Lenburg ME, Trono D (1994) Nef induces CD4 endocytosis: requirement for a critical dileucine motif in the membrane-proximal CD4 cytoplasmic domain. Cell 76(5):853–864PubMedGoogle Scholar
  161. 161.
    Greenberg ME, Bronson S, Lock M, Neumann M, Pavlakis GN, Skowronski J (1997) Co-localization of HIV-1 Nef with the AP-2 adaptor protein complex correlates with Nef-induced CD4 down-regulation. EMBO J 16(23):6964–6976PubMedGoogle Scholar
  162. 162.
    Chaudhuri R, Lindwasser OW, Smith WJ, Hurley JH, Bonifacino JS (2007) Downregulation of CD4 by human immunodeficiency virus type 1 Nef is dependent on clathrin and involves direct interaction of Nef with the AP2 clathrin adaptor. J Virol 81(8):3877–3890PubMedGoogle Scholar
  163. 163.
    Piguet V, Gu F, Foti M, Demaurex N, Gruenberg J, Carpentier JL et al (1999) Nef-induced CD4 degradation: a diacidic-based motif in Nef functions as a lysosomal targeting signal through the binding of beta-COP in endosomes. Cell 97(1):63–73PubMedGoogle Scholar
  164. 164.
    Laguette N, Brégnard C, Benichou S, Basmaciogullari S (2010) Human immunodeficiency virus (HIV) type-1, HIV-2 and simian immunodeficiency virus Nef proteins. Mol Aspects Med 31(5):418–433PubMedGoogle Scholar
  165. 165.
    Schwartz O, Maréchal V, Le Gall S, Lemonnier F, Heard JM (1996) Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein. Nat Med 2(3):338–342PubMedGoogle Scholar
  166. 166.
    Williams M, Roeth JF, Kasper MR, Fleis RI, Przybycin CG, Collins KL (2002) Direct binding of human immunodeficiency virus type 1 Nef to the major histocompatibility complex class I (MHC-I) cytoplasmic tail disrupts MHC-I trafficking. J Virol 76(23):12173–12184PubMedGoogle Scholar
  167. 167.
    Roeth JF, Williams M, Kasper MR, Filzen TM, Collins KL (2004) HIV-1 Nef disrupts MHC-I trafficking by recruiting AP-1 to the MHC-I cytoplasmic tail. J Cell Biol 167(5):903–913PubMedGoogle Scholar
  168. 168.
    Le Gall S, Erdtmann L, Benichou S, Berlioz-Torrent C, Liu L, Benarous R et al (1998) Nef interacts with the mu subunit of clathrin adaptor complexes and reveals a cryptic sorting signal in MHC I molecules. Immunity 8(4):483–495PubMedGoogle Scholar
  169. 169.
    Cohen GB, Gandhi RT, Davis DM, Mandelboim O, Chen BK, Strominger JL et al (1999) The selective downregulation of class I major histocompatibility complex proteins by HIV-1 protects HIV-infected cells from NK cells. Immunity 10(6):661–671PubMedGoogle Scholar
  170. 170.
    Kupzig S, Korolchuk V, Rollason R, Sugden A, Wilde A, Banting G (2003) Bst-2/HM1.24 is a raft-associated apical membrane protein with an unusual topology. Traffic 4(10):694–709PubMedGoogle Scholar
  171. 171.
    Andrew AJ, Kao S, Strebel K (2011) C-terminal hydrophobic region in human bone marrow stromal cell antigen 2 (BST-2)/tetherin protein functions as second transmembrane motif. J Biol Chem 286(46):39967–39981PubMedGoogle Scholar
  172. 172.
    Perez-Caballero D, Zang T, Ebrahimi A, McNatt MW, Gregory DA, Johnson MC et al (2009) Tetherin inhibits HIV-1 release by directly tethering virions to cells. Cell 139(3):499–511PubMedGoogle Scholar
  173. 173.
    Hammonds J, Wang J-J, Yi H, Spearman P (2010) Immunoelectron microscopic evidence for Tetherin/BST2 as the physical bridge between HIV-1 virions and the plasma membrane. PLoS Pathog 6(2):e1000749PubMedGoogle Scholar
  174. 174.
    Andrew AJ, Miyagi E, Kao S, Strebel K (2009) The formation of cysteine-linked dimers of BST-2/tetherin is important for inhibition of HIV-1 virus release but not for sensitivity to Vpu. Retrovirology 6:80PubMedGoogle Scholar
  175. 175.
    Cocka LJ, Bates P (2012) Identification of alternatively translated tetherin isoforms with differing antiviral and signaling activities. PLoS Pathog 8(9):e1002931PubMedGoogle Scholar
  176. 176.
    Rollason R, Korolchuk V, Hamilton C, Schu P, Banting G (2007) Clathrin-mediated endocytosis of a lipid-raft-associated protein is mediated through a dual tyrosine motif. J Cell Sci 120(Pt 21):3850–3858PubMedGoogle Scholar
  177. 177.
    Masuyama N, Kuronita T, Tanaka R, Muto T, Hirota Y, Takigawa A et al (2009) HM1.24 is internalized from lipid rafts by clathrin-mediated endocytosis through interaction with alpha-adaptin. J Biol Chem 284(23):15927–15941PubMedGoogle Scholar
  178. 178.
    Douglas JL, Viswanathan K, McCarroll MN, Gustin JK, Früh K, Moses AV (2009) Vpu directs the degradation of the human immunodeficiency virus restriction factor BST-2/Tetherin via a beta-TrCP-dependent mechanism. J Virol 83(16):7931–7947PubMedGoogle Scholar
  179. 179.
    Mitchell RS, Katsura C, Skasko MA, Fitzpatrick K, Lau D, Ruiz A et al (2009) Vpu antagonizes BST-2-mediated restriction of HIV-1 release via beta-TrCP and endo-lysosomal trafficking. PLoS Pathog 5(5):e1000450PubMedGoogle Scholar
  180. 180.
    Tokarev AA, Munguia J, Guatelli JC (2011) Serine-threonine ubiquitination mediates downregulation of BST-2/tetherin and relief of restricted virion release by HIV-1 Vpu. J Virol 85(1):51–63PubMedGoogle Scholar
  181. 181.
    Goffinet C, Allespach I, Homann S, Tervo H-M, Habermann A, Rupp D et al (2009) HIV-1 antagonism of CD317 is species specific and involves Vpu-mediated proteasomal degradation of the restriction factor. Cell Host Microbe 5(3):285–297PubMedGoogle Scholar
  182. 182.
    Janvier K, Pelchen-Matthews A, Renaud J-B, Caillet M, Marsh M, Berlioz-Torrent C (2011) The ESCRT-0 component HRS is required for HIV-1 Vpu-mediated BST-2/tetherin down-regulation. PLoS Pathog 7(2):e1001265PubMedGoogle Scholar
  183. 183.
    Le Tortorec A, Willey S, Neil SJD (2011) Antiviral inhibition of enveloped virus release by tetherin/BST-2: action and counteraction. Viruses 3(5):520–540PubMedGoogle Scholar
  184. 184.
    Dubé M, Roy BB, Guiot-Guillain P, Binette J, Mercier J, Chiasson A et al (2010) Antagonism of tetherin restriction of HIV-1 release by Vpu involves binding and sequestration of the restriction factor in a perinuclear compartment. PLoS Pathog 6(4):e1000856PubMedGoogle Scholar
  185. 185.
    Schmidt S, Fritz JV, Bitzegeio J, Fackler OT, Keppler OT (2011) HIV-1 Vpu blocks recycling and biosynthetic transport of the intrinsic immunity factor CD317/tetherin to overcome the virion release restriction. MBio 2(3):e00036-11PubMedGoogle Scholar
  186. 186.
    Iwabu Y, Fujita H, Kinomoto M, Kaneko K, Ishizaka Y, Tanaka Y et al (2009) HIV-1 accessory protein Vpu internalizes cell-surface BST-2/tetherin through transmembrane interactions leading to lysosomes. J Biol Chem 284(50):35060–35072PubMedGoogle Scholar
  187. 187.
    Rong L, Zhang J, Lu J, Pan Q, Lorgeoux R-P, Aloysius C et al (2009) The transmembrane domain of BST-2 determines its sensitivity to down-modulation by human immunodeficiency virus type 1 Vpu. J Virol 83(15):7536–7546PubMedGoogle Scholar
  188. 188.
    Mangeat B, Gers-Huber G, Lehmann M, Zufferey M, Luban J, Piguet V (2009) HIV-1 Vpu neutralizes the antiviral factor Tetherin/BST-2 by binding it and directing its beta-TrCP2-dependent degradation. PLoS Pathog 5(9):e1000574PubMedGoogle Scholar
  189. 189.
    Goffinet C, Homann S, Ambiel I, Tibroni N, Rupp D, Keppler OT et al (2010) Antagonism of CD317 restriction of human immunodeficiency virus type 1 (HIV-1) particle release and depletion of CD317 are separable activities of HIV-1 Vpu. J Virol 84(8):4089–4094PubMedGoogle Scholar
  190. 190.
    Miyagi E, Andrew AJ, Kao S, Strebel K (2009) Vpu enhances HIV-1 virus release in the absence of Bst-2 cell surface down-modulation and intracellular depletion. Proc Natl Acad Sci USA 106(8):2868–2873PubMedGoogle Scholar
  191. 191.
    Gupta RK, Mlcochova P, Pelchen-Matthews A, Petit SJ, Mattiuzzo G, Pillay D et al (2009) Simian immunodeficiency virus envelope glycoprotein counteracts tetherin/BST-2/CD317 by intracellular sequestration. Proc Natl Acad Sci USA 106(49):20889–20894PubMedGoogle Scholar
  192. 192.
    Le Tortorec A, Neil SJD (2009) Antagonism to and intracellular sequestration of human tetherin by the human immunodeficiency virus type 2 envelope glycoprotein. J Virol 83(22):11966–11978PubMedGoogle Scholar
  193. 193.
    Jia B, Serra-Moreno R, Neidermyer W, Rahmberg A, Mackey J, Fofana IB et al (2009) Species-specific activity of SIV Nef and HIV-1 Vpu in overcoming restriction by tetherin/BST2. PLoS Pathog 5(5):e1000429PubMedGoogle Scholar
  194. 194.
    Zhang F, Wilson SJ, Landford WC, Virgen B, Gregory D, Johnson MC et al (2009) Nef proteins from simian immunodeficiency viruses are tetherin antagonists. Cell Host Microbe 6(1):54–67PubMedGoogle Scholar
  195. 195.
    Sauter D, Schindler M, Specht A, Landford WN, Munch J, Kim K-A et al (2009) Tetherin-driven adaptation of Vpu and Nef function and the evolution of pandemic and nonpandemic HIV-1 strains. Cell Host Microbe 6(5):409–421PubMedGoogle Scholar
  196. 196.
    Pettit SC, Moody MD, Wehbie RS, Kaplan AH, Nantermet PV, Klein CA et al (1994) The p2 domain of human immunodeficiency virus type 1 Gag regulates sequential proteolytic processing and is required to produce fully infectious virions. J Virol 68(12):8017–8027PubMedGoogle Scholar
  197. 197.
    Byland R (2006) Trafficking of primate lentiviral envelope proteins. PhD Thesis University of LondonGoogle Scholar

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© Springer International Publishing Switzerland 2013

Authors and Affiliations

  1. 1.Cell Biology Unit, MRC Laboratory for Molecular Cell BiologyUniversity College LondonLondonUK

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