Role of multivesicular bodies and their components in the egress of enveloped RNA viruses

As an enveloped virus buds, the nascent viral capsid becomes wrapped in a plasma membrane‐derived lipid envelope, and a membrane fission event is thus necessary to separate the virion from the host cell. This membrane fission event is well characterised in the case of enveloped RNA viruses, where it is promoted by late assembly domains (L‐domains) present at the level of specific viral structural proteins. Research conducted over the past 10 years has demonstrated that L‐domains represent docking sites for cellular proteins essential for the biogenesis of a cellular organelle, the multivesicular body (MVB). In this way, enveloped RNA viruses hijack the MVB components to the cellular site where the budding is executed. This review will focus on the cellular machinery exploited by enveloped RNA viruses in order to be released from infected cells. The role of ubiquitin and lipids in viral budding will also be discussed. Copyright © 2008 John Wiley & Sons, Ltd.

[1]  J. González-Ros,et al.  Protein-promoted membrane domains. , 2008, Biochimica et biophysica acta.

[2]  G. Palù,et al.  Human cytomegalovirus DNA replication: antiviral targets and drugs , 2008, Reviews in medical virology.

[3]  H. Göttlinger,et al.  Efficient and Specific Rescue of Human Immunodeficiency Virus Type 1 Budding Defects by a Nedd4-Like Ubiquitin Ligase , 2008, Journal of Virology.

[4]  W. Sundquist,et al.  NEDD4L Overexpression Rescues the Release and Infectivity of Human Immunodeficiency Virus Type 1 Constructs Lacking PTAP and YPXL Late Domains , 2008, Journal of Virology.

[5]  J. Hurley,et al.  ESCRT complexes and the biogenesis of multivesicular bodies. , 2008, Current opinion in cell biology.

[6]  P. Bieniasz,et al.  Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu , 2008, Nature.

[7]  M. Waterfield,et al.  A selective PIKfyve inhibitor blocks PtdIns(3,5)P2 production and disrupts endomembrane transport and retroviral budding , 2008, EMBO reports.

[8]  J. Martin-Serrano.  The Role of Ubiquitin in Retroviral Egress , 2007, Traffic.

[9]  C. Salata,et al.  Intracellular Trafficking and Maturation of Herpes Simplex Virus Type 1 gB and Virus Egress Require Functional Biogenesis of Multivesicular Bodies , 2007, Journal of Virology.

[10]  J. Luzio,et al.  Ubiquitin-dependent sorting of integral membrane proteins for degradation in lysosomes. , 2007, Current opinion in cell biology.

[11]  Carsten Lambert,et al.  Hepatitis B Virus Maturation Is Sensitive to Functional Inhibition of ESCRT-III, Vps4, and γ2-Adaptin , 2007, Journal of Virology.

[12]  C. Crump,et al.  Herpes Simplex Virus Type 1 Cytoplasmic Envelopment Requires Functional Vps4 , 2007, Journal of Virology.

[13]  G. Barsh,et al.  Spongiform neurodegeneration-associated E3 ligase Mahogunin ubiquitylates TSG101 and regulates endosomal trafficking. , 2007, Molecular biology of the cell.

[14]  S. Gygi,et al.  Targeting of AMSH to Endosomes Is Required for Epidermal Growth Factor Receptor Degradation* , 2007, Journal of Biological Chemistry.

[15]  Matthew West,et al.  Did2 coordinates Vps4-mediated dissociation of ESCRT-III from endosomes , 2006, The Journal of cell biology.

[16]  C. Melief,et al.  Dendritic cells regulate exposure of MHC class II at their plasma membrane by oligoubiquitination. , 2006, Immunity.

[17]  Pier Paolo Di Fiore,et al.  Molecular mechanisms of coupled monoubiquitination , 2006, Nature Cell Biology.

[18]  Amanda Thompson,et al.  A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex. , 2006, Genomics.

[19]  G. Raposo,et al.  Dual loss of ER export and endocytic signals with altered melanosome morphology in the silver mutation of Pmel17. , 2006, Molecular biology of the cell.

[20]  C. Futter,et al.  Distinct roles for Tsg101 and Hrs in multivesicular body formation and inward vesiculation. , 2006, Molecular biology of the cell.

[21]  P. Lehner,et al.  Lysine‐63‐linked ubiquitination is required for endolysosomal degradation of class I molecules , 2006, The EMBO journal.

[22]  S. Emr,et al.  ESCRT-I Core and ESCRT-II GLUE Domain Structures Reveal Role for GLUE in Linking to ESCRT-I and Membranes , 2006, Cell.

[23]  Xuejun Jiang,et al.  Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain. , 2006, Molecular cell.

[24]  H. Stenmark,et al.  Double-sided ubiquitin binding of Hrs-UIM in endosomal protein sorting , 2006, Nature Structural &Molecular Biology.

[25]  G. Raposo,et al.  A lumenal domain-dependent pathway for sorting to intralumenal vesicles of multivesicular endosomes involved in organelle morphogenesis. , 2006, Developmental cell.

[26]  P. Lehner,et al.  Degradation of Endocytosed Epidermal Growth Factor and Virally Ubiquitinated Major Histocompatibility Complex Class I Is Independent of Mammalian ESCRTII* , 2006, Journal of Biological Chemistry.

[27]  Ivan Dikic,et al.  Ubiquitylation and cell signaling , 2005, The EMBO journal.

[28]  Linda Hicke,et al.  Ubiquitin-binding domains , 2005, Nature Reviews Molecular Cell Biology.

[29]  P. Woodman,et al.  Depletion of TSG101 forms a mammalian `Class E' compartment: a multicisternal early endosome with multiple sorting defects , 2005, Journal of Cell Science.

[30]  R. Lamb,et al.  Evidence for a New Viral Late-Domain Core Sequence, FPIV, Necessary for Budding of a Paramyxovirus , 2005, Journal of Virology.

[31]  I. Mellman,et al.  Old lysosomes, new tricks: MHC II dynamics in DCs. , 2005, Trends in immunology.

[32]  U. Schubert,et al.  The trans-Golgi network-associated human ubiquitin-protein ligase POSH is essential for HIV type 1 production. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[33]  P. Bieniasz,et al.  HECT ubiquitin ligases link viral and cellular PPXY motifs to the vacuolar protein-sorting pathway , 2005, The Journal of cell biology.

[34]  I. Amit,et al.  Tal, a Tsg101-specific E3 ubiquitin ligase, regulates receptor endocytosis and retrovirus budding. , 2004, Genes & development.

[35]  G. Raposo,et al.  Endosomes, exosomes and Trojan viruses. , 2004, Trends in microbiology.

[36]  D. Pérez-Caballero,et al.  Context-Dependent Effects of L Domains and Ubiquitination on Viral Budding , 2004, Journal of Virology.

[37]  M. Prevost,et al.  Nedd4.1-mediated ubiquitination and subsequent recruitment of Tsg101 ensure HTLV-1 Gag trafficking towards the multivesicular body pathway prior to virus budding , 2004, Journal of Cell Science.

[38]  A. Adler,et al.  The Rsp5 Ubiquitin Ligase Binds to and Ubiquitinates Members of the Yeast CIN85-Endophilin Complex, Sla1-Rvs167* , 2004, Journal of Biological Chemistry.

[39]  K. Nagashima,et al.  PPPYVEPTAP 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 , 2004, Journal of Virology.

[40]  W. Sundquist,et al.  Ubiquitin recognition by the human TSG101 protein. , 2004, Molecular cell.

[41]  R. N. Harty,et al.  Budding of PPxY-Containing Rhabdoviruses Is Not Dependent on Host Proteins TGS101 and VPS4A , 2004, Journal of Virology.

[42]  Stefan Matile,et al.  Role of LBPA and Alix in Multivesicular Liposome Formation and Endosome Organization , 2004, Science.

[43]  P. De Camilli,et al.  Endophilins interact with Moloney murine leukemia virus Gag and modulate virion production , 2003, Journal of biology.

[44]  W. Weissenhorn,et al.  Lassa Virus Z Protein Is a Matrix Protein and Sufficient for the Release of Virus-Like Particles , 2003, Journal of Virology.

[45]  Linda Hicke,et al.  Regulation of membrane protein transport by ubiquitin and ubiquitin-binding proteins. , 2003, Annual review of cell and developmental biology.

[46]  P. Bieniasz,et al.  A Bipartite Late-Budding Domain in Human Immunodeficiency Virus Type 1 , 2003, Journal of Virology.

[47]  K. Nagashima,et al.  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 , 2003, Journal of Virology.

[48]  J. C. de la Torre,et al.  The small RING finger protein Z drives arenavirus budding: Implications for antiviral strategies , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[49]  A. M. Riley,et al.  Identification of Mammalian Vps24p as an Effector of Phosphatidylinositol 3,5-Bisphosphate-dependent Endosome Compartmentalization* , 2003, Journal of Biological Chemistry.

[50]  W. Weissenhorn,et al.  Lassa Virus Z Protein Is a Matrix Protein Sufficient for the Release of Virus-Like Particles , 2003, Journal of Virology.

[51]  D. Pérez-Caballero,et al.  Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[52]  A. Calistri,et al.  AIP1/ALIX Is a Binding Partner for HIV-1 p6 and EIAV p9 Functioning in Virus Budding , 2003, Cell.

[53]  W. Sundquist,et al.  The Protein Network of HIV Budding , 2003, Cell.

[54]  H. Zentgraf,et al.  The Mason-Pfizer Monkey Virus PPPY and PSAP Motifs Both Contribute to Virus Release , 2003, Journal of Virology.

[55]  R. D. Fisher,et al.  HIV Gag mimics the Tsg101-recruiting activity of the human Hrs protein , 2003, The Journal of cell biology.

[56]  S. Emr,et al.  Vps27 recruits ESCRT machinery to endosomes during MVB sorting , 2003, The Journal of cell biology.

[57]  A. Brech,et al.  Hrs regulates multivesicular body formation via ESCRT recruitment to endosomes , 2003, The Journal of cell biology.

[58]  M. Marsh,et al.  Infectious HIV-1 assembles in late endosomes in primary macrophages , 2003, The Journal of cell biology.

[59]  D. Graham,et al.  Lipid rafts and HIV pathogenesis: virion-associated cholesterol is required for fusion and infection of susceptible cells. , 2003, AIDS research and human retroviruses.

[60]  B. Peterlin,et al.  Nef increases the synthesis of and transports cholesterol to lipid rafts and HIV-1 progeny virions , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[61]  Stanley N Cohen,et al.  TSG101 interaction with HRS mediates endosomal trafficking and receptor down-regulation , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[62]  D. Gerlier,et al.  Virus Entry, Assembly, Budding, and Membrane Rafts , 2003, Microbiology and Molecular Biology Reviews.

[63]  R. Hewson,et al.  Human Immunodeficiency Virus Type 1 Assembly and Lipid Rafts: Pr55gag Associates with Membrane Domains That Are Largely Resistant to Brij98 but Sensitive to Triton X-100 , 2003, Journal of Virology.

[64]  G. V. Vande Woude,et al.  Endosomal dynamics of Met determine signaling output. , 2003, Molecular biology of the cell.

[65]  H. Arst,et al.  YPXL/I Is a Protein Interaction Motif Recognized by Aspergillus PalA and Its Human Homologue, AIP1/Alix , 2003, Molecular and Cellular Biology.

[66]  Ziying Han,et al.  Overlapping Motifs (PTAP and PPEY) within the Ebola Virus VP40 Protein Function Independently as Late Budding Domains: Involvement of Host Proteins TSG101 and VPS-4 , 2003, Journal of Virology.

[67]  S. Emr,et al.  Receptor downregulation and multivesicular-body sorting , 2002, Nature Reviews Molecular Cell Biology.

[68]  Wesley I. Sundquist,et al.  Structure of the Tsg101 UEV domain in complex with the PTAP motif of the HIV-1 p6 protein , 2002, Nature Structural Biology.

[69]  M. Prevost,et al.  The PPPY Motif of Human T-Cell Leukemia Virus Type 1 Gag Protein Is Required Early in the Budding Process , 2002, Journal of Virology.

[70]  L. M. Mansky,et al.  Analysis of Bovine Leukemia Virus Gag Membrane Targeting and Late Domain Function , 2002, Journal of Virology.

[71]  B. Blot,et al.  Alix (ALG-2-interacting Protein X), a Protein Involved in Apoptosis, Binds to Endophilins and Induces Cytoplasmic Vacuolization* , 2002, The Journal of Biological Chemistry.

[72]  A. Calistri,et al.  Late Assembly Domain Function Can Exhibit Context Dependence and Involves Ubiquitin Residues Implicated in Endocytosis , 2002, Journal of Virology.

[73]  E. Freed,et al.  Viral Late Domains , 2002, Journal of Virology.

[74]  W. Sundquist,et al.  Structure and functional interactions of the Tsg101 UEV domain , 2002, The EMBO journal.

[75]  I. Madshus,et al.  Hrs sorts ubiquitinated proteins into clathrin-coated microdomains of early endosomes , 2002, Nature Cell Biology.

[76]  Giorgio F. Gilestro,et al.  The endophilin–CIN85–Cbl complex mediates ligand-dependent downregulation of c-Met , 2002, Nature.

[77]  L. E. Johannessen,et al.  Ubiquitination and proteasomal activity is required for transport of the EGF receptor to inner membranes of multivesicular bodies , 2002, The Journal of cell biology.

[78]  Marius Sudol,et al.  WW and SH3 domains, two different scaffolds to recognize proline‐rich ligands , 2002, FEBS letters.

[79]  E. Freed,et al.  Overexpression of the N-terminal domain of TSG101 inhibits HIV-1 budding by blocking late domain function , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[80]  P. Bieniasz,et al.  HIV-1 and Ebola virus encode small peptide motifs that recruit Tsg101 to sites of particle assembly to facilitate egress , 2001, Nature Medicine.

[81]  E. Freed,et al.  Plasma membrane rafts play a critical role in HIV-1 assembly and release , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[82]  R. N. Harty,et al.  Rhabdoviruses and the Cellular Ubiquitin-Proteasome System: a Budding Interaction , 2001, Journal of Virology.

[83]  Wesley I. Sundquist,et al.  Tsg101 and the Vacuolar Protein Sorting Pathway Are Essential for HIV-1 Budding , 2001, Cell.

[84]  O. W. Lindwasser,et al.  Multimerization of Human Immunodeficiency Virus Type 1 Gag Promotes Its Localization to Barges, Raft-Like Membrane Microdomains , 2001, Journal of Virology.

[85]  H. Issaq,et al.  Modulation of HIV-like particle assembly in vitro by inositol phosphates , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[86]  G. Bu,et al.  Proteasome inhibitors block a late step in lysosomal transport of selected membrane but not soluble proteins. , 2001, Molecular biology of the cell.

[87]  L. Verplank,et al.  Tsg101, a homologue of ubiquitin-conjugating (E2) enzymes, binds the L domain in HIV type 1 Pr55Gag , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[88]  A. Dautry‐Varsat,et al.  Involvement of the ubiquitin/proteasome system in sorting of the interleukin 2 receptor beta chain to late endocytic compartments. , 2001, Molecular biology of the cell.

[89]  T. Mak,et al.  A TSG101/MDM2 regulatory loop modulates MDM2 degradation and MDM2/p53 feedback control. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[90]  P. S. Kim,et al.  Palmitoylation of the HIV-1 envelope glycoprotein is critical for viral infectivity. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[91]  U. Schubert,et al.  Ubiquitination of HIV-1 and MuLV Gag. , 2000, Virology.

[92]  R. N. Harty,et al.  A PPxY motif within the VP40 protein of Ebola virus interacts physically and functionally with a ubiquitin ligase: implications for filovirus budding. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[93]  G. Palù,et al.  A role for ubiquitin ligase recruitment in retrovirus release. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[94]  V. Vogt.  Ubiquitin in retrovirus assembly: actor or bystander? , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[95]  J. Yewdell,et al.  Proteasome inhibition interferes with gag polyprotein processing, release, and maturation of HIV-1 and HIV-2. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[96]  A. Patnaik,et al.  Ubiquitin is part of the retrovirus budding machinery. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[97]  Dzung H. Nguyen,et al.  Evidence for Budding of Human Immunodeficiency Virus Type 1 Selectively from Glycolipid-Enriched Membrane Lipid Rafts , 2000, Journal of Virology.

[98]  S. Goff,et al.  Mutations altering the Moloney murine leukemia virus p12 Gag protein affect virion production and early events of the virus life cycle , 1999, The EMBO journal.

[99]  R. N. Harty,et al.  Late Domain Function Identified in the Vesicular Stomatitis Virus M Protein by Use of Rhabdovirus-Retrovirus Chimeras , 1999, Journal of Virology.

[100]  J. Neefjes,et al.  Multivesicular body morphogenesis requires phosphatidyl-inositol 3-kinase activity , 1999, Current Biology.

[101]  Simon C Watkins,et al.  Equine Infectious Anemia Virus Gag Polyprotein Late Domain Specifically Recruits Cellular AP-2 Adapter Protein Complexes during Virion Assembly , 1998, Journal of Virology.

[102]  A. Chawla,et al.  A functional PtdIns(3)P-binding motif , 1998, Nature.

[103]  Rein Aasland,et al.  FYVE fingers bind PtdIns(3)P , 1998, Nature.

[104]  C. Burd,et al.  Phosphatidylinositol(3)-phosphate signaling mediated by specific binding to RING FYVE domains. , 1998, Molecular cell.

[105]  E. Hunter,et al.  A Proline-Rich Motif (PPPY) in the Gag Polyprotein of Mason-Pfizer Monkey Virus Plays a Maturation-Independent Role in Virion Release , 1998, Journal of Virology.

[106]  L. Arthur,et al.  Ubiquitin Is Covalently Attached to the p6GagProteins of Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus and to the p12Gag Protein of Moloney Murine Leukemia Virus , 1998, Journal of Virology.

[107]  J. Wills,et al.  Equine infectious anemia virus utilizes a YXXL motif within the late assembly domain of the Gag p9 protein , 1997, Journal of virology.

[108]  E. Freed,et al.  p6Gag is required for particle production from full-length human immunodeficiency virus type 1 molecular clones expressing protease , 1995, Journal of virology.

[109]  J. Wills,et al.  Positionally independent and exchangeable late budding functions of the Rous sarcoma virus and human immunodeficiency virus Gag proteins , 1995, Journal of virology.

[110]  K. Takegawa,et al.  Phosphatidylinositol 3-kinase encoded by yeast VPS34 gene essential for protein sorting. , 1993, Science.

[111]  J. Sodroski,et al.  Effect of mutations affecting the p6 gag protein on human immunodeficiency virus particle release. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[112]  A. Ullrich,et al.  Kinase activity controls the sorting of the epidermal growth factor receptor within the multivesicular body , 1990, Cell.

[113]  U. Schubert,et al.  Ubiquitin ligases as therapeutic targets in HIV-1 infection. , 2008, Expert opinion on therapeutic targets.

[114]  Carsten Lambert,et al.  Hepatitis B virus maturation is sensitive to functional inhibition of ESCRT-III, Vps4, and gamma 2-adaptin. , 2007, Journal of virology.

[115]  R. Prange,et al.  Hepatitis B Virus Maturation is Sensitive to Functional Inhibition of , 2007 .

[116]  E. Freed,et al.  Retrovirus budding. , 2004, Virus research.

[117]  R. Hewson,et al.  Human Immunodeficiency Virus Type 1 Assembly and Lipid Rafts: Pr55 gag Associates with Membrane Domains That Are Largely Resistant to Brij98 but Sensitive to Triton X-100 , 2003 .

[118]  R. Hewson,et al.  Human immunodeficiency virus type 1 assembly and lipid rafts: Pr55(gag) associates with membrane domains that are largely resistant to Brij98 but sensitive to Triton X-100. , 2003, Journal of virology.

[119]  H. Göttlinger,et al.  The HIV-1 assembly machine. , 2001, AIDS.

[120]  J J Sixma,et al.  Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules. , 1999, Blood.

[121]  B. Deurs,et al.  Multivesicular bodies in HEp-2 cells are maturing endosomes. , 1993, European journal of cell biology.