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Titolo:
Infection of purified nuclei by adeno-associated virus 2
Autore:
Hansen, J; Qing, K; Srivastava, A;
Indirizzi:
Indiana Univ, Sch Med, Dept Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA Indiana Univ Indianapolis IN USA 46202 mmunol, Indianapolis, IN 46202 USA Indiana Univ, Sch Med, Dept Med, Walther Oncol Ctr, Indianapolis, IN 46202USA Indiana Univ Indianapolis IN USA 46202 col Ctr, Indianapolis, IN 46202USA Indiana Univ, Sch Med, Dept Med, Div Hematol Oncol, Indianapolis, IN 46202USA Indiana Univ Indianapolis IN USA 46202 l Oncol, Indianapolis, IN 46202USA Walther Canc Inst, Indianapolis, IN 46202 USA Walther Canc Inst Indianapolis IN USA 46202 t, Indianapolis, IN 46202 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 4, volume: 4, anno: 2001,
pagine: 289 - 296
SICI:
1525-0016(200110)4:4<289:IOPNBA>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
ADENOASSOCIATED VIRUS; GENE-TRANSFER; TRANSGENE EXPRESSION; PROTEIN; TYPE-2; VECTORS; TRAFFICKING; CORECEPTOR; TRANSPORT; KINASE;
Keywords:
AAV; trafficking; uncoating; nucleus; nuclear pore complex; DNA synthesis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Srivastava, A Indiana Univ, Sch Med, Dept Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA Indiana Univ Indianapolis IN USA 46202 apolis, IN 46202 USA
Citazione:
J. Hansen et al., "Infection of purified nuclei by adeno-associated virus 2", MOL THER, 4(4), 2001, pp. 289-296

Abstract

Adeno-associated virus 2 (AAV), a nonpathogenic human parvovirus, requiresco-infection with a helper virus for its optimal replication. Although AAVpossesses a broad host range, certain cell types lack the machinery necessary for efficient entry into the cell and intracellular trafficking of AAV into the nucleus, where the viral second-strand DNA synthesis must occur before gene expression. We have demonstrated that in less-permissive mouse fibroblasts, the virus fails to transport to the nucleus due to altered endocytic processing. However, relatively little is known about the intracellular site of viral uncoating and transport of the virion across the nuclear envelope. Here, we provide evidence that AAV can efficiently enter intact nuclei purified from both permissive and less-permissive cell types. Furthermore, entry into the nucleus is time- and temperature re-de pendent, but is not saturable and seems to occur independently of the nuclear pore complex. We also demonstrate that purified nuclei contain all of the machinery necessary for uncoating and viral second-strand DNA synthesis even in the absence of a helper virus. These studies provide new insights into the basic biology of AAV and may also have implications for the optimal use of AAV vectors in human gene therapy.

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Documento generato il 18/02/20 alle ore 04:59:53