Differential characteristics of HIV-based versus SIV-based lentiviral vector systems: Gene delivery to neurons and axonal transport of expressed gene.
The differential characteristics of lentiviral vectors based on human and simian immunodeficiency viruses (HIV and SIV) were investigated in rats and monkeys. Each vector was injected into the striatum, and the expression patterns of the marker gene green fluorescent protein (GFP) were analyzed in the basal ganglia. With respect to the capability of gene delivery to neural cells, the HIV-based vector exhibited a higher tropism to neurons than to astroglias in the striatum, and vice versa for the SIV-based vector. The preferential direction of axonal transport of striatally expressed GFP was also examined in the present study. The HIV-based vector allowed for both anterograde transport via the striatopallidal and striatonigral pathways and retrograde transport via the nigrostriatal pathway. The GFP labeling of axon terminals through anterograde transport was apparent regardless of the animal species, while that of neuronal cell bodies through retrograde transport was much more prominent in monkeys than in rats. As for the SIV-based vector, on the other hand, evidence for anterograde transport was obtained much more markedly in monkeys than in rats, and only weak or no retrograde transport occurred in either monkeys or rats. Our results indicate that HIV-based, but not SIV-based, lentiviral vectors possess the high tropism to neurons and permit retrograde transport of an expressed gene, especially in primates. The latter property might carry a potential benefit in gene therapy for Parkinson's disease, as stereotaxic injections of the vectors could be performed into the striatum, spatially larger than the substantia nigra, with greater certainty.
Kitagawa
Ryo
R
Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo 113-8602, Japan.
Miyachi
Shigehiro
S
Hanawa
Hideki
H
Takada
Masahiko
M
Shimada
Takashi
T
D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D003342:Corpus Striatum / Q000166:cytology / Q000821:virology; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D005822:Genetic Vectors / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006678:HIV / Q000502:physiology*; D000882:Haplorhini; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D051381:Rats; D017208:Rats, Wistar; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D014161:Transduction, Genetic / Q000379:methods; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D049452:Green Fluorescent Proteins; D014446:Tyrosine 3-Monooxygenase