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Pseudotyping lentiviral vectors with the wild-type measles virus glycoproteins improves titer and selectivity

Abstract

We pseudotyped HIV-1 vectors with cytoplasmic tail-truncated envelope glycoproteins of a wild-type (WT) measles virus (MV). The particles entered the lymphatic cells exclusively through the signaling lymphocyte activation molecule (SLAM, CD150), whereas particles pseudotyped with the MV vaccine strain glycoproteins also recognized the ubiquitous membrane cofactor protein (CD46) as receptor and had less specific cell entry. MVWT-HIV vectors reached titers of 108 t.u. ml−1, which were up to 10-fold higher than those of MVVac-HIV vectors, and discriminated between SLAM-positive and SLAM-negative cells, also in mixed cell cultures. As these vectors transduce primary human cells more efficiently than vesicular stomatitis virus-G pseudotyped vectors do, they are promising candidates for gene transfer to human lymphocytes and certain epithelial cells.

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References

  1. Cronin J, Zhang XY, Reiser J . Altering the tropism of lentiviral vectors through pseudotyping. Curr Gene Ther 2005; 5: 387–398.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sandrin V, Russell SJ, Cosset FL . Targeting retroviral and lentiviral vectors. Curr Top Microbiol Immunol 2003; 281: 137–178.

    CAS  PubMed  Google Scholar 

  3. Cockrell AS, Kafri T . Gene delivery by lentivirus vectors. Mol Biotechnol 2007; 36: 184–204.

    Article  CAS  PubMed  Google Scholar 

  4. Funke S, Maisner A, Muhlebach MD, Koehl U, Grez M, Cattaneo R et al. Targeted cell entry of lentiviral vectors. Mol Ther 2008; 16: 1427–1436.

    Article  CAS  PubMed  Google Scholar 

  5. Frecha C, Costa C, Negre D, Gauthier E, Russell SJ, Cosset FL et al. Stable transduction of quiescent T-cells without induction of cycle progression by a novel lentiviral vector pseudotyped with measles virus glycoproteins. Blood 2008; 112: 4843–4852.

    Article  CAS  PubMed  Google Scholar 

  6. Vongpunsawad S, Oezgun N, Braun W, Cattaneo R . Selectively receptor-blind measles viruses: identification of residues necessary for SLAM- or CD46-induced fusion and their localization on a new hemagglutinin structural model. J Virol 2004; 78: 302–313.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Leonard VH, Sinn PL, Hodge G, Miest T, Devaux P, Oezguen N et al. Measles virus blind to its epithelial cell receptor remains virulent in rhesus monkeys but cannot cross the airway epithelium and is not shed. J Clin Invest 2008; 118: 2448–2458.

    CAS  PubMed Central  PubMed  Google Scholar 

  8. Yanagi Y, Takeda M, Ohno S . Measles virus: cellular receptors, tropism and pathogenesis. J Gen Virol 2006; 87 (Part 10): 2767–2779.

    Article  CAS  PubMed  Google Scholar 

  9. Condack C, Grivel JC, Devaux P, Margolis L, Cattaneo R . Measles virus vaccine attenuation: suboptimal infection of lymphatic tissue and tropism alteration. J Infect Dis 2007; 196: 541–549.

    Article  CAS  PubMed  Google Scholar 

  10. Veillette A . Immune regulation by SLAM family receptors and SAP-related adaptors. Nat Rev Immunol 2006; 6: 56–66.

    Article  CAS  PubMed  Google Scholar 

  11. Tahara M, Takeda M, Shirogane Y, Hashiguchi T, Ohno S, Yanagi Y . Measles virus infects both polarized epithelial and immune cells by using distinctive receptor-binding sites on its hemagglutinin. J Virol 2008; 82: 4630–4637.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Takeda M, Tahara M, Hashiguchi T, Sato TA, Jinnouchi F, Ueki S et al. A human lung carcinoma cell line supports efficient measles virus growth and syncytium formation via a SLAM- and CD46-independent mechanism. J Virol 2007; 81: 12091–12096.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Takeda M, Takeuchi K, Miyajima N, Kobune F, Ami Y, Nagata N et al. Recovery of pathogenic measles virus from cloned cDNA. J Virol 2000; 74: 6643–6647.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Singh M, Cattaneo R, Billeter MA . A recombinant measles virus expressing hepatitis B virus surface antigen induces humoral immune responses in genetically modified mice. J Virol 1999; 73: 4823–4828.

    CAS  PubMed Central  PubMed  Google Scholar 

  15. Liebert UG, Flanagan SG, Loffler S, Baczko K, ter Meulen V, Rima BK . Antigenic determinants of measles virus hemagglutinin associated with neurovirulence. J Virol 1994; 68: 1486–1493.

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Tiscornia G, Singer O, Verma IM . Production and purification of lentiviral vectors. Nat Protoc 2006; 1: 241–245.

    Article  CAS  PubMed  Google Scholar 

  17. Clavel F, Charneau P . Fusion from without directed by human immunodeficiency virus particles. J Virol 1994; 68: 1179–1185.

    CAS  PubMed Central  PubMed  Google Scholar 

  18. Cathomen T, Naim HY, Cattaneo R . Measles viruses with altered envelope protein cytoplasmic tails gain cell fusion competence. J Virol 1998; 72: 1224–1234.

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Tatsuo H, Ono N, Tanaka K, Yanagi Y . SLAM (CDw150) is a cellular receptor for measles virus. Nature 2000; 406: 893–897.

    Article  CAS  PubMed  Google Scholar 

  20. Buchholz CJ, Schneider U, Devaux P, Gerlier D, Cattaneo R . Cell entry by measles virus: long hybrid receptors uncouple binding from membrane fusion. J Virol 1996; 70: 3716–3723.

    CAS  PubMed Central  PubMed  Google Scholar 

  21. Takeuchi K, Miyajima N, Nagata N, Takeda M, Tashiro M . Wild-type measles virus induces large syncytium formation in primary human small airway epithelial cells by a SLAM(CD150)-independent mechanism. Virus Res 2003; 94: 11–16.

    Article  CAS  PubMed  Google Scholar 

  22. Navaratnarajah CK, Vongpunsawad S, Oezguen N, Stehle T, Braun W, Hashiguchi T et al. Dynamic interaction of the measles virus hemagglutinin with its receptor signaling lymphocytic activation molecule (SLAM, CD150). J Biol Chem 2008; 283: 11763–11771.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Schneider-Schaulies S, Schneider-Schaulies J, Niewiesk S, Ter Meulen V . Measles virus: immunomodulation and cell tropism as pathogenicity determinants. Med Microbiol Immunol 2002; 191: 83–87.

    Article  CAS  PubMed  Google Scholar 

  24. Welstead GG, Hsu EC, Iorio C, Bolotin S, Richardson CD . Mechanism of CD150 (SLAM) down regulation from the host cell surface by measles virus hemagglutinin protein. J Virol 2004; 78: 9666–9674.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Overbaugh J, Miller AD, Eiden MV . Receptors and entry cofactors for retroviruses include single and multiple transmembrane-spanning proteins as well as newly described glycophosphatidylinositol-anchored and secreted proteins. Microbiol Mol Biol Rev 2001; 65: 371–389, table.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by grant BU 1301/2-1 of the priority Program ‘Mechanisms of gene vector entry and persistence’ of the Deutsche Forschungsgemeinschaft to CJB and KC. SF was supported by the graduate study program ‘GK1172 Biologicals’ of the Goethe University Frankfurt a.M. We thank Julia Brynza for excellent technical assistance and wish to acknowledge V Leonard (Mayo Clinic, USA) and Y Yanagi (Kyushu University, Japan) for the F and H expression plasmids and CHO-SLAM cells, respectively, and J Schneider-Schaulies (University of Würzburg, Germany) for the K83 hybridoma cell line.

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Correspondence to C J Buchholz.

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Funke, S., Schneider, I., Glaser, S. et al. Pseudotyping lentiviral vectors with the wild-type measles virus glycoproteins improves titer and selectivity. Gene Ther 16, 700–705 (2009). https://doi.org/10.1038/gt.2009.11

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