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The impact of DNA viruses and their ...

Stilwell, Jackie Lynn.

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The impact of DNA viruses and their virion shells on cellular gene expression.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	The impact of DNA viruses and their virion shells on cellular gene expression./
作者:	Stilwell, Jackie Lynn.
面頁冊數:	204 p.
附註:	Director: R. Jude Samulski.
Contained By:	Dissertation Abstracts International63-03B.
標題:	Biology, Genetics. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3047078
ISBN:	0493610510

The impact of DNA viruses and their virion shells on cellular gene expression.
Stilwell, Jackie Lynn.

The impact of DNA viruses and their virion shells on cellular gene expression. - 204 p.

Director: R. Jude Samulski.

Thesis (Ph.D.)--The University of North Carolina at Chapel Hill, 2002.

Roles of the virion shell in viral pathogenesis are relatively unknown. Yet, the use of viral vectors in human gene transfer experiments requires an understanding of these interactions. In this study, we utilized DNA micro arrays to identify genes whose expression is modulated during pathogenic adenovirus (Ad) or non-pathogenic adeno associated virus (AAV) infections. Responses to wild type viruses, recombinant vectors or empty virion particles were compared. Interestingly, AAV shells induced nearly the full compliment of changes elicited by the intact virus. Furthermore, the cellular genes affected correlated with a non-pathogenic response, with anti-proliferative genes being induced as a cluster. In contrast, Ad infection yielded a much broader response, including induction of immune and stress-response genes associated with pathogenic effects. Unlike AAV, the number of genes induced by empty Ad capsids was significantly reduced in comparison with intact viral infection. Of critical importance to human therapeutic approaches using Ad, even capsids continued to induce many of the same stress-response genes modulated by the first generation recombinant viruses.

ISBN: 0493610510Subjects--Topical Terms:

1017730
Biology, Genetics.

The impact of DNA viruses and their virion shells on cellular gene expression.
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245 1 0 $a The impact of DNA viruses and their virion shells on cellular gene expression.
300 $a 204 p.
500 $a Director: R. Jude Samulski.
500 $a Source: Dissertation Abstracts International, Volume: 63-03, Section: B, page: 1150.
502 $a Thesis (Ph.D.)--The University of North Carolina at Chapel Hill, 2002.
520 $a Roles of the virion shell in viral pathogenesis are relatively unknown. Yet, the use of viral vectors in human gene transfer experiments requires an understanding of these interactions. In this study, we utilized DNA micro arrays to identify genes whose expression is modulated during pathogenic adenovirus (Ad) or non-pathogenic adeno associated virus (AAV) infections. Responses to wild type viruses, recombinant vectors or empty virion particles were compared. Interestingly, AAV shells induced nearly the full compliment of changes elicited by the intact virus. Furthermore, the cellular genes affected correlated with a non-pathogenic response, with anti-proliferative genes being induced as a cluster. In contrast, Ad infection yielded a much broader response, including induction of immune and stress-response genes associated with pathogenic effects. Unlike AAV, the number of genes induced by empty Ad capsids was significantly reduced in comparison with intact viral infection. Of critical importance to human therapeutic approaches using Ad, even capsids continued to induce many of the same stress-response genes modulated by the first generation recombinant viruses.
520 $a Because the largest cluster of genes induced in an AAV infection, including infection with empty capsid, were involved in cell proliferation this was further studied. Using FACS analysis along with a cell line deficient in the cell surface molecule used for initial AAV2 binding, and antibodies that block AAV internalization, we were able to demonstrate a correlation of AAV2 virion attachment to a G2 cell cycle delay. When similar studies were performed using other AAV serotypes, a G2 cell cycle delay was not observed, further distinguishing the role of the type 2 virion in the virus life.
520 $a This study establishes mRNA expression profiles for both AAV and Ad vectors impacting studies of AAV biology, and the use of both AAV and Ad for gene therapy. These expression profiles provide the foundation for studies of other modified vectors based on these viruses, assessment of transgenes expressed by these vectors upon cells, in vivo toxicology studies, and identification of molecular mechanisms of host response to infection.
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