Positive and negative effects of adenovirus type 5 helper functions on adeno-associated virus type 5 (AAV5) protein accumulation govern AAV5 virus production
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作者:
Nayak, Ramnath
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Univ Missouri, Sch Med, Life Sci Ctr, Dept Mol Microbiol & Immunol, Columbia, MO 65211 USAUniv Missouri, Sch Med, Life Sci Ctr, Dept Mol Microbiol & Immunol, Columbia, MO 65211 USA
Nayak, Ramnath
[1
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Pintel, David J.
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Univ Missouri, Sch Med, Life Sci Ctr, Dept Mol Microbiol & Immunol, Columbia, MO 65211 USAUniv Missouri, Sch Med, Life Sci Ctr, Dept Mol Microbiol & Immunol, Columbia, MO 65211 USA
Pintel, David J.
[1
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机构:
[1] Univ Missouri, Sch Med, Life Sci Ctr, Dept Mol Microbiol & Immunol, Columbia, MO 65211 USA
Full replication of adeno-associated virus type 5 (AAV5) is sustained by adenovirus type 5 (AM) helper functions E1a, E1b, E2a, E4Orf6, and virus-associated (VA) RNA; however, their combined net enhancement of AAV5 replication was comprised of both positive and negative individual effects. Although Ad5 E4Orf6 was required for AAV5 genomic DNA replication, it also functioned together with E1b to degrade de novo-expressed, preassembled AAV5 capsid proteins and Rep52 in a proteosome-dependent manner. VA RNA enhanced accumulation of AAV5 protein, overcoming the degradative effects of E4Orf6, and was thus required to restore adequate amounts of AAV5 proteins necessary to achieve efficient virus production.
机构:
Univ N Carolina, Gene Therapy Ctr, Chapel Hill, NC 27599 USA
Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USAUniv N Carolina, Gene Therapy Ctr, Chapel Hill, NC 27599 USA
Hewitt, F. Curtis
Li, Chengwen
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Univ N Carolina, Gene Therapy Ctr, Chapel Hill, NC 27599 USAUniv N Carolina, Gene Therapy Ctr, Chapel Hill, NC 27599 USA
Li, Chengwen
Gray, Steven J.
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Univ N Carolina, Gene Therapy Ctr, Chapel Hill, NC 27599 USAUniv N Carolina, Gene Therapy Ctr, Chapel Hill, NC 27599 USA
Gray, Steven J.
Cockrell, Shelley
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Univ Pittsburgh, Interdisciplinary Biomed Grad Program, Pittsburgh, PA 15261 USAUniv N Carolina, Gene Therapy Ctr, Chapel Hill, NC 27599 USA
Cockrell, Shelley
Washburn, Michael
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Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USAUniv N Carolina, Gene Therapy Ctr, Chapel Hill, NC 27599 USA
Washburn, Michael
Samulski, R. Jude
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Univ N Carolina, Gene Therapy Ctr, Chapel Hill, NC 27599 USA
Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA
Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USAUniv N Carolina, Gene Therapy Ctr, Chapel Hill, NC 27599 USA