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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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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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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DOI: https://doi.org/10.1038/gt.2009.11
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