Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA 90089, USA.
Hum Gene Ther. 2011 Oct;22(10):1281-91. doi: 10.1089/hum.2010.196. Epub 2011 Jun 13.
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.
慢病毒载体（LVs）假型化带有甲病毒包膜蛋白，最近因其作为基因传递工具的潜力而引起了相当大的关注。我们报告了使用源自 Aura 病毒（AURA）的包膜糖蛋白假型化的人类免疫缺陷病毒 1 型（HIV-1）衍生的 LVs 的生产。我们发现 AURA-糖蛋白假型化的 LVs 使用 C 型凝集素（DC-SIGN 和 L-SIGN）作为附着因子。这些与 DC-SIGN 的相互作用是特异性的，如通过抑制测定确定的，并且似乎通过 pH 依赖性途径促进转导。AURA 假型化的 LVs 用于转导单核细胞衍生的树突状细胞（DC），并且转导被证明是由 DC-SIGN 介导的，如用 DC-SIGN 和 L-SIGN 抗体和酵母甘露聚糖进行竞争抑制所说明的。与包被有来自水疱性口炎病毒和辛德毕斯病毒的糖蛋白的 LVs 的比较表明，携带 AURA 糖蛋白的 LVs 可能有助于对 DC 进行基因修饰，以研究 DC 生物学和基于 DC 的免疫疗法。
