+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Specific patterns of defective HSV-1 gene transfer in the adult central nervous system: implications for gene targeting



Specific patterns of defective HSV-1 gene transfer in the adult central nervous system: implications for gene targeting



Experimental Neurology 130(1): 127-140



Viral vectors are a means by which genes can be delivered to specific sites in the adult central nervous system. Nevertheless, the interaction between the viral vector and cells of the nervous system, which forms the basis for specific gene transfer, is not well understood. In this study a nonreplicating defective herpes simplex virus type 1 vector, expressing the marker gene lacZ, was stereotaxically injected at varying titers into the rat central nervous system. Three sites were targeted: the caudate nucleus, dentate gyrus, and cerebellar cortex, and the resulting patterns of beta-galactosidase activity were examined. Many cells of neuronal and glial morphology, and of differing neuronal subtypes, expressed beta-galactosidase at each of the injection sites. However, beta-galactosidase activity was also detected in distant secondary brain areas, the neurons of which make afferent connections with the primary sites. This strongly suggested that the retrograde transport of defective virus was the basis for the enzyme activity observed at a distance. Moreover, retrograde transport to secondary sites was found to be highly selective and restricted to certain retrograde neuroanatomical pathways in a specific and titer dependent fashion. The pathways observed were predominantly, but not exclusively, monoaminergic in origin. This finding is supported by reports of specific tropism by HSV for monoaminergic circuits in experimental encephalitis and transneuronal tracing studies. Our observations suggest that certain functional neuronal populations, which are permissive for the retrograde transfer of defective HSV-1 vectors, might be specifically targeted for gene transfer using this approach. Conversely, a knowledge of the pathways permissive for viral uptake, retrograde transfer, and subsequent gene expression will be essential in order to predict the consequences of gene transfer using viral vectors.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 009442932

Download citation: RISBibTeXText

PMID: 7821388

DOI: 10.1006/exnr.1994.1192


Related references

Human immunodeficiency virus tat gene transfer to the murine central nervous system using a replication-defective herpes simplex virus vector stimulates transforming growth factor beta 1 gene expression. Proceedings Of The National Academy Of Sciences Of The United States Of America. 93(12): 6073-6078, 1996

Promoters and serotypes: targeting of adeno-associated virus vectors for gene transfer in the rat central nervous system in vitro and in vivo. Experimental Physiology 90(1): 53-59, 2004

Growth factor enhanced retroviral gene transfer to the adult central nervous system. Gene Therapy 7(13): 1103-1111, 2000

Somatic gene transfer in the adult central nervous system Practical and theoretical issues. Society for Neuroscience Abstracts 20(1-2): 1505, 1994

Aspartoacylase gene transfer to the mammalian central nervous system with therapeutic implications for Canavan disease. Annals of Neurology 48(1): 27-38, 2000

In vivo gene transfer into the adult mammalian central nervous system by continuous injection of plasmid DNA-cationic liposome complex. Brain Research 780(1): 119-128, 1998

Gene targeting and gene transfer studies of the plasminogen/plasmin system: implications in thrombosis, hemostasis, neointima formation, and atherosclerosis. Faseb Journal 9(10): 934-938, 1995

In vivo gene transfer to the central nervous system Prospects for gene therapy in Huntingtons disease. Semaine des Hopitaux 70(29-30): 908-910, 1994

From gene transfer to gene therapy in lysosomal storage diseases affecting the central nervous system. Annals of Medicine 33(1): 28-36, 2001

Gene therapy of the central nervous system: general considerations on viral vectors for gene transfer into the brain. Revue Neurologique 170(12): 727-738, 2015

Expression patterns of the survival of motor neuron gene and gene product in the mammalian central nervous system. American Journal of Human Genetics 59(4 SUPPL ): A149, 1996

Defective viral vectors as agents for gene transfer in the nervous system. Journal Of Neuroscience Methods. 71(1): 125-132, 1997

Expression patterns of the SMN gene, the human spinal muscular atrophy determining gene, in the mammalian central nervous system. Society for Neuroscience Abstracts 22(1-3): 235, 1996

Patterns of gene expression in the developing adult sea urchin central nervous system reveal multiple domains and deep-seated neural pentamery. Evolution and Development 4(3): 189-204, 2002

Adenovirus-mediated gene transfer and expression of human b-glucuronidase gene in the liver, spleen, and central nervous system in mucopolysaccharidosis type VII mice. Proceedings of the National Academy of Sciences of the United States of America 94: 87-92, 1997