Abstract

Adeno-associated virus (AAV) is a non-pathogenic human DNA virus that can be propagated either as a lytic virus or as a provirus. For lytic growth AAV requires the presence of a helper virus (either adenovirus or herpes simplex virus). In the absence of the helper virus, AAV readily produces cells in which one or more copies of AAV DNA are carried in the proviral form. If a latently infected cell line is superinfected with the helper, the proviral sequences are efficiently rescued and proceed through a normal AAV lytic cycle. These properties of AAV make it potentially useful both as a transducing vector for mammalian cells and also as a model for studying the biology of latent viral infections. In our previous work, we demonstrated that AAV sequences which have been cloned into a prokaryotic vector (pBR322) can be rescued from the recombinant plasmid in vivo in a fashion similar to the rescue of AAV proviral sequences from host chromosomes. We have used this infectious AAV plasmid to study the genetics of AAV as well as to construct AAV derived vectors. In this study, we propose to continue this work and also to study the mechanism of AAV DNA integration.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM035723-03
Application #
3288834
Study Section
Virology Study Section (VR)
Project Start
1986-02-01
Project End
1991-01-31
Budget Start
1988-02-01
Budget End
1989-01-31
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
State University New York Stony Brook
Department
Type
Schools of Medicine
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794

  Publications

Brister, J R; Muzyczka, N (2000) Mechanism of Rep-mediated adeno-associated virus origin nicking. J Virol 74:7762-71
Klein, R L; Muir, D; King, M A et al. (1999) Long-term actions of vector-derived nerve growth factor or brain-derived neurotrophic factor on choline acetyltransferase and Trk receptor levels in the adult rat basal forebrain. Neuroscience 90:815-21
Brister, J R; Muzyczka, N (1999) Rep-mediated nicking of the adeno-associated virus origin requires two biochemical activities, DNA helicase activity and transesterification. J Virol 73:9325-36
Zhou, X; Zolotukhin, I; Im, D S et al. (1999) Biochemical characterization of adeno-associated virus rep68 DNA helicase and ATPase activities. J Virol 73:1580-90
Klein, R L; Lewis, M H; Muzyczka, N et al. (1999) Prevention of 6-hydroxydopamine-induced rotational behavior by BDNF somatic gene transfer. Brain Res 847:314-20
Gavin, D K; Young Jr, S M; Xiao, W et al. (1999) Charge-to-alanine mutagenesis of the adeno-associated virus type 2 Rep78/68 proteins yields temperature-sensitive and magnesium-dependent variants. J Virol 73:9433-45
Klein, R L; McNamara, R K; King, M A et al. (1999) Generation of aberrant sprouting in the adult rat brain by GAP-43 somatic gene transfer. Brain Res 832:136-44
Ni, T H; McDonald, W F; Zolotukhin, I et al. (1998) Cellular proteins required for adeno-associated virus DNA replication in the absence of adenovirus coinfection. J Virol 72:2777-87
Zhou, X; Muzyczka, N (1998) In vitro packaging of adeno-associated virus DNA. J Virol 72:3241-7
Klein, R L; Meyer, E M; Peel, A L et al. (1998) Neuron-specific transduction in the rat septohippocampal or nigrostriatal pathway by recombinant adeno-associated virus vectors. Exp Neurol 150:183-94

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