Abstract
Vpx is coded almost exclusively by members of the SIVSM/HIV-2 lineage of primate lentiviruses, it is incorporated into virion particles and is thus present during the early phases of infection of target cells. While Vpx exerts no detectable function during the infection of most cell types, it potently counteracts a cellular restriction that targets incoming lentiviruses specifically in myeloid cells. As a consequence of this function, Vpx improves the efficiency of lentiviral infection of dendritic cells (DCs), macrophages, and monocytes. Here, we describe how the positive function exerted by Vpx during the early phases of infection of myeloid cells can be used to augment the efficiency of lentiviral vector-mediated gene transfer in these cells.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Tristem M, Marshall C, Karpas A, Petrik J, Hill F (1990) Origin of vpx in lentiviruses. Nature 347:341–342
Banapour B, Marthas ML, Ramos RA, Lohman BL, Unger RE, Gardner MB, Pedersen NC, Luciw PA (1991) Identification of viral determinants of macrophage tropism for simian immunodeficiency virus SIVmac. J Virol 65:5798–5805
Marcon L, Michaels F, Hattori N, Fargnoli K, Gallo RC, Franchini G (1991) Dispensable role of the human immunodeficiency virus type 2 Vpx protein in viral replication. J Virol 65:3938–3942
Goujon C, Arfi V, Pertel T, Luban J, Lienard J, Rigal D, Darlix JL, Cimarelli A (2008) Characterization of simian immunodeficiency virus SIVSM/human immunodeficiency virus type 2 Vpx function in human myeloid cells. J Virol 82:12335–12345
Goujon C, Jarrosson-Wuilleme L, Bernaud J, Rigal D, Darlix JL, Cimarelli A (2006) With a little help from a friend: increasing HIV transduction of monocyte-derived dendritic cells with virion-like particles of SIV(MAC). Gene Ther 13:991–994
Goujon C, Riviere L, Jarrosson-Wuilleme L, Bernaud J, Rigal D, Darlix JL, Cimarelli A (2007) SIVSM/HIV-2 Vpx proteins promote retroviral escape from a proteasome-dependent restriction pathway present in human dendritic cells. Retrovirology 4:2
Fujita M, Otsuka M, Miyoshi M, Khamsri B, Nomaguchi M, Adachi A (2008) Vpx is critical for reverse transcription of the human immunodeficiency virus type 2 genome in macrophages. J Virol 82:7752–7756
Bergamaschi A, Ayinde D, David A, Le Rouzic E, Morel M, Collin G, Descamps D, Damond F, Brun-Vezinet F, Nisole S, Margottin-Goguet F, Pancino G, Transy C (2009) The human immunodeficiency virus type 2 Vpx protein usurps the CUL4A-DDB1 DCAF1 ubiquitin ligase to overcome a postentry block in macrophage infection. J Virol 83:4854–4860
Srivastava S, Swanson SK, Manel N, Florens L, Washburn MP, Skowronski J (2008) Lentiviral Vpx accessory factor targets VprBP/DCAF1 substrate adaptor for cullin 4 E3 ubiquitin ligase to enable macrophage infection. PLoS Pathog 4:e1000059
Sharova N, Wu Y, Zhu X, Stranska R, Kaushik R, Sharkey M, Stevenson M (2008) Primate lentiviral Vpx commandeers DDB1 to counteract a macrophage restriction. PLoS Pathog 4:e1000057
Laguette N, Sobhian B, Casartelli N, Ringeard M, Chable-Bessia C, Segeral E, Yatim A, Emiliani S, Schwartz O, Benkirane M (2011) SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature 474(7353):654–657
Rice GI, Bond J, Asipu A, Brunette RL, Manfield IW, Carr IM, Fuller JC, Jackson RM, Lamb T, Briggs TA, Ali M, Gornall H, Couthard LR, Aeby A, Attard-Montalto SP, Bertini E, Bodemer C, Brockmann K, Brueton LA, Corry PC, Desguerre I, Fazzi E, Cazorla AG, Gener B, Hamel BC, Heiberg A, Hunter M, van der Knaap MS, Kumar R, Lagae L, Landrieu PG, Lourenco CM, Marom D, McDermott MF, van der Merwe W, Orcesi S, Prendiville JS, Rasmussen M, Shalev SA, Soler DM, Shinawi M, Spiegel R, Tan TY, Vanderver A, Wakeling EL, Wassmer E, Whittaker E, Lebon P, Stetson DB, Bonthron DT, Crow YJ (2009) Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response. Nat Genet 41:829–832
Berger G, Durand S, Goujon C, Nguyen XN, Cordeil S, Darlix JL, Cimarelli A (2011) A simple, versatile and efficient method to genetically modify human monocyte-derived dendritic cells with HIV-1-derived lentiviral vectors. Nat Protoc 6:806–816
Naldini L, Blomer U, Gallay P, Ory D, Mulligan R, Gage FH, Verma IM, Trono D (1996) In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272:263–267
Mangeot PE, Duperrier K, Negre D, Boson B, Rigal D, Cosset FL, Darlix JL (2002) High levels of transduction of human dendritic cells with optimized SIV vectors. Mol Ther 5:283–290
Acknowledgments
Work in our laboratory is supported by grants from the Agence Nationale de Recherche sur le SIDA (ANRS), SIDACTION, Fondation pour la Recherche Médicale (FRM), INSERM, and Ecole Normale Supérieure de Lyon (ENS-Lyon). A.C. is supported by the Centre National de la Recherche Sciéntifique (CNRS).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Berger, G., Cimarelli, A. (2014). SIVSM/HIV-2 Vpx Proteins: Function and Uses in the Infection of Primary Myeloid Cells. In: Vicenzi, E., Poli, G. (eds) Human Retroviruses. Methods in Molecular Biology, vol 1087. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-670-2_13
Download citation
DOI: https://doi.org/10.1007/978-1-62703-670-2_13
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-62703-669-6
Online ISBN: 978-1-62703-670-2
eBook Packages: Springer Protocols