Abstract
The primary vectors of choice for gene therapy applications have been oncoretroviruses due to their simple genetic organization and their ability to integrate into the host cell genome without incurring cellular toxicity (ANDERSON 1998). However, these vectors require cell division for integration to occur (MILLER et al. 1990) due to a requirement for nuclear envelope breakdown to allow entry of the viral integration complex into the nucleus (ROE et al. 1993). This presents a major obstacle for in vivo or ex vivo transduction of non-dividing cells such as neurons, hepatocytes, muscle fibres, quiescent lymphocytes, and haematopoietic stem cells, as these cells are either inaccessible by such vectors, or must be manipulated in potentially detrimental ways to facilitate cell division and vector integration. For this reason, interest in recent years has turned to lentiviruses, due to their ability to infect and integrate in certain types of non-dividing cells (WEINBERG et al. 1991; BUKRINSKY et al. 1993; LEWIS and EMERMAN 1994). One lentivirus on which much work has been focused to derive vectors for gene therapy has been HIV-1, as it is the best characterized of the lentiviruses. The remainder of this review will focus on the properties of HIV-1 that allow it to efficiently infect non-dividing cells, and on the development of progressively safer and more efficient HIV-1-derived vectors over the past few years.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Aiken C (1997) Pseudotyping human immunodeficiency virus type 1 (HIV-1) by the glycoprotein of vesicular stomatitis virus targets HIV-1 entry to an endocytic pathway and suppresses both the requirement for Nef and the sensitivity to cyclosporin A. J Virol 71:5871–5877
Aiken C, Trono D (1995) Nef stimulates human immunodeficiency virus type 1 proviral DNA synthesis. J Virol 69:5048–5056
Anderson WF (1998) Human Gene Ther Nature 392:25–30
Arya SK, Zamani M, Kundra P (1998) Human immunodeficiency virus type 2 lentivirus vectors for gene transfer: expression and potential for helper virus-free packaging. Hum Gene Ther 9:1371–1380
Bartz SR, Emerman M (1999) Human immunodeficiency virus type 1 Tat induces apoptosis and increases sensitivity to apoptotic signals by up-regulating FLICE/caspase-8. J Virol 73:1956–1963
Bartz SR, Vodicka MA (1997) Production of high-titer human immunodeficiency virus type 1 pseudo-typed with vesicular stomatitis virus glycoprotein. Methods 12:337–342
Bensadoun JC, Deglon N, Tseng JL, Ridet JL, Zum AD, Aebischer P (2000) Lentiviral vectors as a gene delivery system in the mouse midbrain: cellular and behavioral improvements in a 6-OHDA model of Parkinson’s disease using GDNF. Exp Neurol 164:15–24
Binley J, Moore JP (1997) HIV-cell fusion. The viral mousetrap. Nature 387:346–348
Blomer U, Naldini L, Kafri T, Trono D, Verma IM, Gage FH (1997) Highly efficient and sustained gene transfer in adult neurons with a lentivirus vector. J Virol 71:6641–6649
Bosch A, Perret E, Desmaris N, Trono D, Heard JM (2000) Reversal of pathology in the entire brain of mucopolysaccharidosis type VII mice after lentivirus-mediated gene transfer. Hum Gene Ther 11:1139–1150
Bukovsky AA, Song JP, Naldini L (1999) Interaction of human immunodeficiency virus-derived vectors with wild-type virus in transduced cells. J Virol 73:7087–7092
Bukovsky A, Dull T, Follenzi A, Nguyen M, Kelly M, McGuinness R, Malech H, Naldini L (2000) Novel design of HIV-based vector system with no viral sequences overlap between packaging and transfer vector constructs. Mol Ther 1:S139
Bukrinsky MI, Haffar OK (1999) HIV-1 nuclear import: in search of a leader. Front Biosci 4:772–781
Bukrinsky MI, Haggerty S, Dempsey MP, Sharova N, Adzhubel A, Spitz L, Lewis P, Goldfarb D, Emerman M, Stevenson M (1993) A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. Nature 365:666–669
Bukrinsky MI, Sharova N, Dempsey MP, Stanwick TL, Bukrinskaya AG, Haggerty S, Stevenson M (1992) Active nuclear import of human immunodeficiency virus type 1 preintegration complexes. Proc Natl Acad Sci USA 89:6580–6584
Burns JC, Friedmann T, Driever W, Burrascano M, Yee JK (1993) Vesicular stomatitis virus G glycoprotein pseudotyped retroviral vectors: concentration to very high titre and efficient gene transfer into mammalian and nonmammalian cells. Proc Natl Acad Sci USA 90:8033–8037
Cassan M, Delaunay N, Vaquero C, Rousset JP (1994) Translational frameshifting at the gag-pol junction of human immunodeficiency virus type 1 is not increased in infected T-lymphoid cells. J Virol 68:1501–1508
Chameau P, Mirambeau G, Roux P, Paulous S, Buc H, Clavel F (1994) HIV-1 reverse transcription. A termination step at the center of the genome. J Mol Biol 241:651–662
Chinnasamy D, Chinnasamy N, Enriquez MJ, Otsu M, Morgan RA, Candotti F (2000) Lentiviral-mediated gene transfer into human lymphocytes: role of HIV-1 accessory proteins. Blood 96:1309–1316
Clapham PR, Weiss RA (1997) Immunodeficiency viruses. Spoilt for choice of co-receptors. Nature 388:230–231
Clever JL, Parslow TG (1997) Mutant human immunodeficiency virus type 1 genomes with defects in RNA dimerization or encapsidation. J Virol 71:3407–3414
Coffin J, Hughes SH, Varmus HE (2000) Retroviruses. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
Consiglio A, Quattrini A, Martino S, Bensadoun JC, Dolcetta D, Trojani A, Benaglia G, Marchesini S, Cestari V, Oliverio A, Bordignon C, Naldini L (2001) In vivo gene therapy of metachromatic leukodystrophy in lentiviral vectors: correlation of neuropathology and protection against learning impairments in affected mice. Nat Med 7:310–316
Corbeau P, Kraus G, Wong-Staal F (1998) Transduction of human macrophages using a stable HIV-1/HIV-2-derived gene delivery system. Gene Ther 5:99–104
Costello E, Munoz M, Buetti E, Meylan PR, Diggelmann H, Thali M (2000) Gene transfer into stimulated and unstimulated T lymphocytes by HIV-1-derived lentiviral vectors. Gene Ther 7:596–604
Cullen BR (1998) HIV-1 auxiliary proteins: making connections in a dying cell. Cell 93:685–692
Dalgleish AG, Beverley PC, Clapham PR, Crawford DH, Greaves MF, Weiss RA (1984) The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 312:763–767
Deglon N, Tseng JL, Bensadoun JC, Zum AD, Arsenijevic Y, Pereira DA, Zufferey R, Trono D, Aebischer P (2000) Self-inactivating lentiviral vectors with enhanced transgene expression as potential gene transfer system in Parkinson’s disease. Hum Gene Ther 11:179–190
Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Di Marzio P, Marmon S, Sutton RE, Hill CM, Davis CB, Peiper SC, Schall TJ, Littman DR, Landau NR (1996) Identification of a major co-receptor for primary isolates of HIV-1. Nature 381:661–666
Deng HK, Unutmaz D, KewalRamani VN, Littman DR (1997) Expression cloning of new receptors used by simian and human immunodeficiency viruses. Nature 388:296–300
Dettenhofer M, Cen S, Carlson BA, Kleiman L, Yu XF (2000) Association of human immunodeficiency virus type 1 Vif with RNA and its role in reverse transcription. J Virol 74:8938–8945
Dull T, Zufferey R, Kelly M, Mandel RJ, Nguyen M, Trono D, Naldini L (1998) A third-generation lentivirus vector with a conditional packaging system. J Virol 72:8463–8471
Emerman M (2000) Learning from lentiviruses. Nat Genet 24:8–9
Emerman M, Malim MH (1998) HIV-1 regulatory/accessory genes: keys to unraveling viral and host cell biology. Science 280:1880–1884
Federico M (1999) Lentiviruses as gene delivery vectors. Curr Opin Biotechnol 10:448–453
Feng Y, Broder CC, Kennedy PE, Berger EA (1996a) HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272:872–877
Feng YX, Copeland TD, Henderson LE, Gorelick RJ, Bosche WJ, Levin JG, Rein A (1996b) HIV-1 nucleocapsid protein induces “maturation” of dimeric retroviral RNA in vitro. Proc Natl Acad Sci USA 93:7577–7581
Follenzi A, Ailles LE, Bakovic S, Geuna M, Naldini L (2000) Gene transfer by lentiviral vectors is limited by nuclear translocation and rescued by HIV-1 pol sequences. Nat Genet 25:217–222
Fouchier RA, Meyer BE, Simon JH, Fischer U, Albright AV, Gonzalez-Scarano F, Malim MH (1998) Interaction of the human immunodeficiency virus type 1 Vpr protein with the nuclear pore complex. J Virol 72:6004–6013
Frankel AD, Young JA (1998) HIV-1: fifteen proteins and an RNA. Ann Rev Biochem 67:1–25
Freed EO, Martin MA (1994)HIV-1 infection of non-dividing cells. Nature 369:107–108
Gallay P, Hope T, Chin D, Trono D (1997) HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway. Proc Natl Acad Sci USA 94:9825–9830
Gallay P, Stitt V, Mundy C, Oettinger M, Trono D (1996) Role of the karyopherin pathway in human immunodeficiency virus type 1 nuclear import. J Virol 70:1027–1032
Gallichan WS, Kafri T, Krahl T, Verma IM, Sarvetnick N (1998) Lentivirus-mediated transduction of islet grafts with interleukin 4 results in sustained gene expression and protection from insulitis. Hum Gene Ther 9:2717–2726
Gasmi M, Glynn J, Jin MJ, Jolly DJ, Yee JK, Chen ST (1999) Requirements for efficient production and transduction of human immunodeficiency virus type 1-based vectors. J Virol 73:1828–1834
Goh WC, Rogel ME, Kinsey CM, Michael SF, Fultz PN, Nowak MA, Hahn BH, Emerman M (1998) HIV-1 Vpr increases viral expression by manipulation of the cell cycle: a mechanism for selection of Vpr in vivo. Nat Med 4:65–71
Grande A, Piovani B, Aiuti A, Ottolenghi S, Mavilio F, Ferrari G (1999) Transcriptional targeting of retroviral vectors to the erythroblastic progeny of transduced hematopoietic stem cells. Blood 93:3276–3285
Guenechea G, Gan OI, Inamitsu T, Dorrell C, Pereira DS, Kelly M, Naldini L, Dick JE (2000) Transduction of human CD34+ CD38-bone marrow and cord blood-derived SCID-repopulating cells with third-generation lentiviral vectors. Mol Ther 1:566–573
He J, Choe S, Walker R, Di Marzio P, Morgan DO, Landau NR (1995) Human immunodeficiency virus type 1 viral protein R (Vpr) arrests cells in the G2 phase of the cell cycle by inhibiting p34cdc2 activity. J Virol 69:6705–6711
Hill CM, Deng H, Unutmaz D, KewalRamani VN, Bastiani L, Gorny MK, Zolla-Pazner S, Littman DR (1997) Envelope glycoproteins from human immunodeficiency virus types 1 and 2 and simian immunodeficiency virus can use human CCR5 as a coreceptor for viral entry and make direct CD4-dependent interactions with this chemokine receptor. J Virol 71:6296–6304
Hill CP, Worthylake D, Bancroft DP, Christensen AM, Sundquist WI (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
Kafri T, Blomer U, Peterson DA, Gage FH, Verma IM (1997) Sustained expression of genes delivered directly into liver and muscle by lentiviral vectors. Nat Genet 17:314–317
Kanki PJ, Travers KU, MBoup S, Hsieh CC, Marlink RG, Gueye-NDiaye A, Siby T, Thior I, Hernandez-Avila M, Sankale JL (1994) Slower heterosexual spread of HIV-2 than HIV-1. Lancet 343:943–946
Katz RA, Skalka AM (1994) The retroviral enzymes. Ann Rev Biochem 63:133–173
Kerkau T, Bacik I, Bennink JR, Yewdell JW, Hunig T, Schimpl A, Schubert U (1997) The human immunodeficiency virus type 1 (HIV-1) Vpu protein interferes with an early step in the biosynthesis of major histocompatibility complex (MHC) class I molecules. J Exp Med 185:1295–1305
Kim VN, Mitrophanous K, Kingsman SM, Kingsman AJ (1998) Minimal requirement for a lentivirus vector based on human immunodeficiency virus type 1. J Virol 72:811–816
Kinoshita S, Chen BK, Kaneshima H, Nolan GP (1998) Host control of HIV-1 parasitism in T cells by the nuclear factor of activated T cells. Cell 95:595–604
Kondo E, Gottlinger HG (1996) A conserved LXXLF sequence is the major determinant in p6gag required for the incorporation of human immunodeficiency virus type 1 Vpr. J Virol 70:159–164
Kordower JH, Bloch J, Ma SY, Chu Y, Palfi S, Roitberg BZ, Emborg M, Hantraye P, Deglon N, Aebischer P (1999) Lentiviral gene transfer to the nonhuman primate brain.Exp Neurol 160:1–16
Kordower JH, Emborg ME, Bloch J, Ma SY, Chu Y, Leventhal L, McBride J, Chen E-Y, Palfi S, Roitberg BZ, Brown WD, Holden JE, Pyzalski R, Taylor MD, Carvey P, Ling Z, Trono D, Hantraye P, Deglon N, Aebischer P (2000) Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson’s disease. Science 290:767–773
Korin YD, Zack JA (1998) Progression to the Gib phase of the cell cycle is required for completion of human immunodeficiency virus type 1 reverse transcription in T cells. J Virol 72:3161–3168
Korin YD, Zack JA (1999) Nonproductive human immunodeficiency virus type 1 infection in nucleoside-treated G0 lymphocytes. J Virol 73:6526–6532
Lamb RA, Pinto LH (1997) Do Vpu and Vpr of human immunodeficiency virus type 1 and NB of influenza B virus have ion channel activities in the viral life cycles? Virology 229:1–11
Landau NR, Page KA, Littman DR (1991) Pseudotyping with human T-cell leukemia virus type I broadens the human immunodeficiency virus host range. J Virol 65:162–169
Lewis PF, Emerman M (1994) Passage through mitosis is required for oncoretroviruses but not for the human immunodeficiency virus. J Virol 68:510–516
Madani N, Kabat D (1998) An endogenous inhibitor of human immunodeficiency virus in human lymphocytes is overcome by the viral Vif protein. J Virol 72:10251–10255
Malim MH, Hauber J, Le SY, Maizel JV, Cullen BR (1989) The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA. Nature 338: 254–257
Mangasarian A, Foti M, Aiken C, Chin D, Carpentier JL, Trono D (1997a) The HIV-1 Nef protein acts as a connector with sorting pathways in the Golgi and at the plasma membrane. Immunity 6:67–77
Mangasarian A, Trono D (1997b) The multifaceted role of HIV Nef. Res Virol pp 30–33
Marlink R, Kanki P, Thior I, Travers K, Eisen G, Siby T, Traore I, Hsieh CC, Dia MC, Gueye EH (1994) Reduced rate of disease development after HIV-2 infection as compared to HIV-1. Science 265:1587–1590
May C, Rivella S, Callegari J, Heller G, Gaensler KM, Luzzatto L, Sadelain M (2000) Therapeutic haemoglobin synthesis in beta-thalassaemic mice expressing lentivirus-encoded human beta-globin. Nature 406:82–86
Miller DG, Adam MA, Miller AD (1990) Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection. Mol Cell Biol 10:4239–4242
Miyoshi H, Blomer U, Takahashi M, Gage FH, Verma IM (1998) Development of a self-inactivating lentivirus vector. J Virol 72:8150–8157
Miyoshi H, Smith KA, Mosier DE, Verma IM, Torbett BE (1999) Transduction of human CD34+ cells that mediate long-term engraftment of NOD/SCID mice by HIV vectors. Science 283:682–686
Miyoshi H, Takahashi M, Gage FH, Verma IM (1997) Stable and efficient gene transfer into the retina using an HIV-based lentiviral vector. Proc Natl Acad Sci USA 94:10319–10323
Naldini L (1998) Lentiviruses as gene transfer agents for delivery to non-dividing cells. Curr Opin Biotechnol 9:457–463
Naldini L, Blomer U, Gage FH, Trono D, Verma IM (1996a) Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector. Proc Natl Acad Sci USA 93:11382–11388
Naldini L, Blomer U, Gallay P, Ory D, Mulligan R, Gage FH, Verma IM, Trono D (1996b) In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272: 263–267
Neville M, Stutz F, Lee L, Davis LI, Rosbash M (1997) The importin-beta family member Crmlp bridges the interaction between Rev and the nuclear pore complex during nuclear export. Curr Biol 7:767–775
Page KA, Landau NR, Littman DR (1990) Construction and use of a human immunodeficiency virus vector for analysis of virus infectivity. J Virol 64:5270–5276
Park F, Ohashi K, Kay MA (2000) Therapeutic levels of human factor VIII and IX using HIV-1-based lentiviral vectors in mouse liver. Blood 96:1173–1176
Parolin C, Dorfman T, Palu G, Gottlinger H, Sodroski J (1994) Analysis in human immunodeficiency virus type 1 vectors of cis-acting sequences that affect gene transfer into human lymphocytes. J Virol 68:3888–3895
Poeschla E, Corbeau P, Wong-Staal F (1996) Development of HIV vectors for anti-HIV gene therapy. Proc Natl Acad Sci USA 93:11395–11399
Poeschla E, Gilbert J, Li X, Huang S, Ho A, Wong-Staal F (1998) Identification of a human immunodeficiency virus type 2 (HIV-2) encapsidation determinant and transduction of nondividing human cells by HIV-2-based lentivirus vectors. J Virol 72:6527–6536
Popov S, Rexach M, Zybarth G, Reiling N, Lee MA, Ratner L, Lane CM, Moore MS, Blobel G, Bukrinsky M (1998) Viral protein R regulates nuclear import of the HIV-1 pre-integration complex. EMBO J 17:909–917
Roe T, Reynolds TC, Yu G, Brown PO (1993) Integration of murine leukemia virus DNA depends on mitosis. EMBO J 12:2099–2108
Schneider R, Campbell M, Nasioulas G, Felber BK, Pavlakis GN (1997) Inactivation of the human immunodeficiency virus type 1 inhibitory elements allows Rev-independent expression of Gag and Gag/protease and particle formation. J Virol 71:4892–4903
Schubert U, Anton LC, Bacik I, Cox JH, Bour S, Bennink JR, Orlowski M, Strebel K, Yewdell JW (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 72:2280–2288
Schwartz O, Marechal V, Danos O, Heard JM (1995) Human immunodeficiency virus type 1 Nef increases the efficiency of reverse transcription in the infected cell. J Virol 69:4053–4059
Simon JH, Malim MH (1996) The human immunodeficiency virus type 1 Vif protein modulates the postpenetration stability of viral nucleoprotein complexes. J Virol 70:5297–5305
Stevenson M (2000) HIV nuclear import: What’s the flap? Nat Med 6:626–628
Takahashi M, Miyoshi H, Verma IM, Gage FH (1999) Rescue from photoreceptor degeneration in the rd mouse by human immunodeficiency virus vector-mediated gene transfer. J Virol 73:7812–7816
Tiganos E, Yao XJ, Friborg J, Daniel N, Cohen EA (1997) Putative alpha-helical structures in the human immunodeficiency virus type 1 Vpu protein and CD4 are involved in binding and degradation of the CD4 molecule. J Virol 71:4452–4460
Unutmaz D, KewalRamani VN, Marmon S, Littman DR (1999) Cytokine signals are sufficient for HIV-1 infection of resting human T lymphocytes. J Exp Med 189:1735–1746
Valentin A, Aldrovandi G, Zolotukhin AS, Cole SW, Zack JA, Pavlakis GN, Felber BK (1997) Reduced viral load and lack of CD4 depletion in SCID-hu mice infected with Rev-independent clones of human immunodeficiency virus type 1. J Virol 71:9817–9822
Vigna E, Naldini L (2000) Lentiviral vectors: excellent tools for experimental gene transfer and promising candidates for gene therapy. J Gene Med 2:308–316
Vodicka MA, Koepp DM, Silver PA, Emerman M (1998) HIV-1 Vpr interacts with the nuclear transport pathway to promote macrophage infection. Genes Dev 12:175–185
von Schwedler UK, Stemmler TL, Klishko VY, Li S, Albertine KH, Davis DR, Sundquist WI (1998) Proteolytic refolding of the HIV-1 capsid protein amino-terminus facilitates viral core assembly. EMBO J 17:1555–1568
Weinberg JB, Matthews TJ, Cullen BR, Malim MH (1991) Productive human immunodeficiency virus type 1 (HIV-1) infection of nonproliferating human monocytes. J Exp Med 174:1477–1482
Wilcox DA, Olsen JC, Ishizawa L, Griffith M, White GC (1999) Integrin alphallb promoter-targeted expression of gene products in megakaryocytes derived from retrovirus-transduced human hematopoietic cells. Proc Natl Acad Sci USA 96:9654–9659
Willey RL, Maldarelli F, Martin MA, Strebel K (1992) Human immunodeficiency virus type 1 Vpu protein induces rapid degradation of CD4. J Virol 66:7193–7200
Wyatt R, Sodroski J (1998) The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. Science 280:1884–1888
Zack JA, Arrigo SJ, Weitsman SR, Go AS, Haislip A, Chen IS (1990) HIV-1 entry into quiescent primary lymphocytes: molecular analysis reveals a labile, latent viral structure. Cell 61:213–222
Zack JA, Haislip AM, Krogstad P, Chen IS (1992) Incompletely reverse-transcribed human immunodeficiency virus type 1 genomes in quiescent cells can function as intermediates in the retroviral life cycle. J Virol 66:1717–1725
Zennou V, Petit C, Guetard D, Nerhbass U, Montagnier L, Chameau P (2000) HIV-1 genome nuclear import is mediated by a central DNA flap. Cell 101:173–185
Zufferey R, Donello JE, Trono D, Hope TJ (1999) Woodchuck hepatitis virus posttranscriptional regulatory element enhances expression of transgenes delivered by retroviral vectors. J Virol 73: 2886–2892
Zufferey R, Dull T, Mandel RJ, Bukovsky A, Quiroz D, Naldini L, Trono D (1998) Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery. J Virol 72:9873–9880
Zufferey R, Nagy D, Mandel RJ, Naldini L, Trono D (1997) Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo. Nat Biotechnol 15:871–875
zur Megede J, Chen MC, Doe B, Schaefer M, Greer CE, Selby M, Otten GR, Barnett SW (2000) Increased expression and immunogenicity of sequence-modified human immunodeficiency virus type 1 gag gene. J Virol 74:2628–2635
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Ailles, L.E., Naldini, L. (2002). HIV-1-Derived Lentiviral Vectors. In: Trono, D. (eds) Lentiviral Vectors. Current Topics in Microbiology and Immunology, vol 261. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-56114-6_2
Download citation
DOI: https://doi.org/10.1007/978-3-642-56114-6_2
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-62667-8
Online ISBN: 978-3-642-56114-6
eBook Packages: Springer Book Archive