Fink D J, Sternberg L R, Weber P C, Mata M, Goins W F, Glorioso J C
Department of Neurology, University of Michigan, Ann Arbor 48105.
Hum Gene Ther. 1992 Feb;3(1):11-9. doi: 10.1089/hum.1992.3.1-11.
Stereotactic inoculation of a herpes simplex virus (HSV) gene transfer vector into the hippocampus and caudate of rat brain resulted in limited and transient viral replication and the establishment of latency. Virus attenuation was achieved by insertional inactivation of a viral gene, Us3. Insertion of a lacZ reporter gene, under the control of the HSV glycoprotein C (gC) late gene promoter, allowed viral replication to be monitored in vivo. Unlike unattenuated virus, the Us3::pgC-lacZ recombinant caused little apparent damage to normal hippocampal morphology. Transient lacZ expression was detected in a considerable population of neurons of the dentate gyrus following hippocampal injection, whereas few positively staining neurons were present within the caudate after injection at that site. Latency-associated transcripts, the hallmark of latent infection, were detected in the brain 10 months after injection. This recombinant virus may be useful as a gene transfer vector for long-term expression of foreign genes in the central nervous system.
将单纯疱疹病毒（HSV）基因转移载体立体定向接种到大鼠脑海马体和尾状核中，导致病毒复制有限且短暂，并建立了潜伏状态。通过病毒基因Us3的插入失活实现了病毒减毒。在HSV糖蛋白C（gC）晚期基因启动子的控制下插入lacZ报告基因，使得能够在体内监测病毒复制。与未减毒的病毒不同，Us3::pgC-lacZ重组体对正常海马形态几乎没有明显损害。海马注射后，在齿状回的相当一部分神经元中检测到短暂的lacZ表达，而在该部位注射后尾状核内几乎没有阳性染色的神经元。注射10个月后，在脑中检测到潜伏感染的标志——潜伏相关转录本。这种重组病毒可能作为一种基因转移载体，用于在中枢神经系统中长期表达外源基因。
