Masuda M, Hanson C A, Dugger N V, Robbins D S, Wilt S G, Ruscetti S K, Hoffman P M
Laboratory of Molecular Oncology, National Cancer Institute, Frederick, Maryland 21702, USA.
J Virol. 1997 Aug;71(8):6168-73. doi: 10.1128/JVI.71.8.6168-6173.1997.
PVC-211 murine leukemia virus (MuLV) causes neurodegenerative disease following inoculation of neonatal, but not adult, mice and rats. It was previously shown that tropism for brain capillary endothelial cells (CEC) was a determinant of the viral neuropathogenicity. In this study, we demonstrate that host age-dependent replication of PVC-211 MuLV in vivo occurs in CEC in the brain as well as in other organs, such as the liver, kidney, and heart. In contrast, primary explant cultures of CEC derived from brains and livers of adult and neonatal rats could be infected by PVC-211 MuLV, suggesting that the age-dependent susceptibility was abrogated in vitro. Although CEC were generally less susceptible to MuLV-mediated gene transduction than fibroblasts, treatment of CEC with 2-deoxyglucose followed by inoculation of a PVC-211 MuLV-pseudotyped vector in the absence of heparin improved the transduction efficiency. These observations support the possibility that PVC-211 MuLV may be useful for establishing models of CEC gene transduction.
PVC - 211鼠白血病病毒(MuLV)在接种新生小鼠和大鼠而非成年小鼠和大鼠后会引发神经退行性疾病。先前的研究表明,对脑毛细血管内皮细胞(CEC)的嗜性是病毒神经致病性的一个决定因素。在本研究中,我们证明PVC - 211 MuLV在体内的宿主年龄依赖性复制发生在脑内的CEC以及其他器官,如肝脏、肾脏和心脏中。相比之下,来自成年和新生大鼠脑和肝脏的CEC原代外植体培养物可被PVC - 211 MuLV感染,这表明在体外消除了年龄依赖性易感性。尽管CEC通常比成纤维细胞对MuLV介导的基因转导更不敏感,但用2 - 脱氧葡萄糖处理CEC,然后在不存在肝素的情况下接种PVC - 211 MuLV假型载体可提高转导效率。这些观察结果支持PVC - 211 MuLV可能有助于建立CEC基因转导模型的可能性。