Pseudotyping lentiviral vectors with the wild-type measles virus glycoproteins improves titer and selectivity.
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. MV(WT)-HIV vectors reached titers of 10(8) t.u. ml(-1), which were up to 10-fold higher than those of MV(Vac)-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.
Funke
S
S
Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany.
Schneider
I C
IC
Glaser
S
S
Mühlebach
M D
MD
Moritz
T
T
Cattaneo
R
R
Cichutek
K
K
Buchholz
C J
CJ
D001402:B-Lymphocytes / Q000821:virology; D002460:Cell Line; D004847:Epithelial Cells / Q000821:virology; D018390:Gene Targeting / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics*; D008459:Measles virus / Q000235:genetics*; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D014162:Transfection; D014759:Viral Envelope Proteins / Q000235:genetics*; D056189:Viral Tropism / Q000235:genetics; D053586:Virus Internalization
D047908:Intracellular Signaling Peptides and Proteins; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D014759:Viral Envelope Proteins