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Pseudotyping lentiviral vectors with aura virus envelope glycoproteins for DC-SIGN-mediated transduction of dendritic cells.

Abstract
Lentiviral vectors (LVs) pseudotyped with envelope proteins of alphaviruses have recently attracted considerable interest for their potential as gene delivery tools. We report the production of human immunodeficiency virus type 1 (HIV-1)-derived LVs pseudotyped with envelope glycoproteins derived from the Aura virus (AURA). We found that the AURA-glycoprotein-pseudotyped LVs use C-type lectins (DC-SIGN and L-SIGN) as attachment factors. These interactions with DC-SIGN are specific as determined by inhibition assays and appear to facilitate transduction through a pH-dependent pathway. AURA-pseudotyped LVs were used to transduce monocyte-derived dendritic cells (DCs) and the transduction was shown to be DC-SIGN mediated, as illustrated by competitive inhibition with DC-SIGN and L-SIGN antibodies and yeast mannan. Comparisons with LVs enveloped with glycoproteins derived from vesicular stomatitis virus and Sindbis virus suggest that AURA-glycoprotein-bearing LVs might be useful to genetically modify DCs for the study of DC biology and DC-based immunotherapy.
AuthorsSteven Froelich, April Tai, Katie Kennedy, Adnan Zubair, Pin Wang
JournalHuman gene therapy (Hum Gene Ther) Vol. 22 Issue 10 Pg. 1281-91 (Oct 2011) ISSN: 1557-7422 [Electronic] United States
PMID21452926 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins, C-Type
  • Receptors, Cell Surface
  • Viral Envelope Proteins
  • Green Fluorescent Proteins
Topics
  • Alphavirus (metabolism)
  • Animals
  • Cell Adhesion Molecules (genetics, metabolism)
  • Dendritic Cells (metabolism)
  • Gene Transfer Techniques
  • Genes, vpr (genetics)
  • Genetic Engineering (methods)
  • Genetic Vectors (biosynthesis, genetics)
  • Green Fluorescent Proteins (genetics, metabolism)
  • HEK293 Cells
  • HIV-1 (genetics)
  • Humans
  • Lectins, C-Type (genetics, metabolism)
  • Mice
  • Microscopy, Confocal
  • NIH 3T3 Cells
  • Plasmids (genetics)
  • Receptors, Cell Surface (genetics, metabolism)
  • Transduction, Genetic (methods)
  • Viral Envelope Proteins (metabolism)

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