Hosoya Noriaki, Miura Toshiyuki, Kawana-Tachikawa Ai, Koibuchi Tomohiko, Shioda Tatsuo, Odawara Takashi, Nakamura Tetsuya, Kitamura Yoshihiro, Kano Munehide, Kato Atsushi, Hasegawa Mamoru, Nagai Yoshiyuki, Iwamoto Aikichi
Division of Infectious Diseases, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
J Med Virol. 2008 Mar;80(3):373-82. doi: 10.1002/jmv.21052.
Immuno-genetherapy using dendritic cells (DCs) can be applied to human immunodeficiency virus type 1 (HIV-1) infection. Sendai virus (SeV) has unique features such as cytoplasmic replication and high protein expression as a vector for genetic manipulation. In this study, we compared the efficiency of inducing green fluorescent protein (GFP) and HIV-1 gene expression in human monocyte-derived DCs between SeV and adenovirus (AdV). Human monocyte-derived DCs infected with SeV showed the maximum gene expression 24 hr after infection at a multiplicity of infection (MOI) of 2. Although SeV vector showed higher cytopathic effect on DCs than AdV, SeV vector induced maximum gene expression earlier and at much lower MOI. In terms of cell surface phenotype, both SeV and AdV vectors induced DC maturation. DCs infected with SeV as well as AdV elicited HIV-1 specific T-cell responses detected by interferon gamma (IFN-gamma) enzyme-linked immunospot (Elispot). Our data suggest that SeV could be one of the reliable vectors for immuno-genetherapy for HIV-1 infected patients.
利用树突状细胞(DCs)的免疫基因治疗可应用于1型人类免疫缺陷病毒(HIV-1)感染。仙台病毒(SeV)作为一种基因操作载体,具有诸如胞质复制和高蛋白表达等独特特征。在本研究中,我们比较了仙台病毒(SeV)和腺病毒(AdV)在人单核细胞衍生DCs中诱导绿色荧光蛋白(GFP)和HIV-1基因表达的效率。感染SeV的人单核细胞衍生DCs在感染复数(MOI)为2时,感染后24小时显示出最大基因表达。尽管SeV载体对DCs的细胞病变效应比AdV更高,但SeV载体诱导最大基因表达的时间更早,且所需MOI低得多。就细胞表面表型而言,SeV和AdV载体均诱导DC成熟。感染SeV以及AdV的DCs引发了通过干扰素γ(IFN-γ)酶联免疫斑点法(Elispot)检测到的HIV-1特异性T细胞反应。我们的数据表明,SeV可能是用于HIV-1感染患者免疫基因治疗的可靠载体之一。