東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

Herpes simplex virus DNA replication...

Cui, Can.

Linked to FindBook

Google Book

Amazon

博客來

Herpes simplex virus DNA replication and microRNA expression: Molecular pharmacological, computational, and genetic approaches.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Herpes simplex virus DNA replication and microRNA expression: Molecular pharmacological, computational, and genetic approaches./
Author:	Cui, Can.
Description:	187 p.
Notes:	Adviser: Donald M. Coen.
Contained By:	Dissertation Abstracts International68-02B.
Subject:	Biology, Genetics. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3251263

Herpes simplex virus DNA replication and microRNA expression: Molecular pharmacological, computational, and genetic approaches.
Cui, Can.

Herpes simplex virus DNA replication and microRNA expression: Molecular pharmacological, computational, and genetic approaches. - 187 p.

Adviser: Donald M. Coen.

Thesis (Ph.D.)--Harvard University, 2007.

The interaction between the catalytic subunit, Pol, and the processivity subunit, UL42, of herpes simplex virus 1 (HSV-1) DNA polymerase has been characterized structurally and mutationally, and is a potential target for novel antiviral drugs. Our laboratory developed and validated an assay for small molecules that could interrupt the interaction of UL42 and a Pol-derived peptide, and identified one "hit", namely BP5, which inhibited UL42-stimulated long-chain DNA synthesis by Pol in vitro , and exhibited little inhibition of polymerase activity by Pol alone. I showed that BP5 specifically inhibited the physical interaction of Pol and UL42, and also inhibited viral replication at concentrations below those that caused cytotoxic effects. To investigate the antiviral mechanism of BP5, a resistant mutant was isolated after multiple-cycle selection. A candidate BP5-resistance (BP5r) mutation was identified by DNA sequencing. This point mutation in the TATA box of UL42 was shown to confer BP5r by genetic experiments using a bacterial artificial chromosome (BAC) of HSV-1 strain KOS that I generated and characterized. Structure-activity relationships of BP5 were studied and a less cytotoxic analog, which retains considerable antiviral activity via the same mechanism, was identified. This new compound may be useful for selection of other resistant mutants.Subjects--Topical Terms:

1017730
Biology, Genetics.

Herpes simplex virus DNA replication and microRNA expression: Molecular pharmacological, computational, and genetic approaches.
LDR:03319nam 2200313 a 45 001 943654
005 20110520
008 110520s2007 ||||||||||||||||| ||eng d
035 $a (UMI)AAI3251263
035 $a AAI3251263
040 $a UMI $c UMI
100 1 $a Cui, Can. $3 1267688
245 1 0 $a Herpes simplex virus DNA replication and microRNA expression: Molecular pharmacological, computational, and genetic approaches.
300 $a 187 p.
500 $a Adviser: Donald M. Coen.
500 $a Source: Dissertation Abstracts International, Volume: 68-02, Section: B, page: 0753.
502 $a Thesis (Ph.D.)--Harvard University, 2007.
520 $a The interaction between the catalytic subunit, Pol, and the processivity subunit, UL42, of herpes simplex virus 1 (HSV-1) DNA polymerase has been characterized structurally and mutationally, and is a potential target for novel antiviral drugs. Our laboratory developed and validated an assay for small molecules that could interrupt the interaction of UL42 and a Pol-derived peptide, and identified one "hit", namely BP5, which inhibited UL42-stimulated long-chain DNA synthesis by Pol in vitro , and exhibited little inhibition of polymerase activity by Pol alone. I showed that BP5 specifically inhibited the physical interaction of Pol and UL42, and also inhibited viral replication at concentrations below those that caused cytotoxic effects. To investigate the antiviral mechanism of BP5, a resistant mutant was isolated after multiple-cycle selection. A candidate BP5-resistance (BP5r) mutation was identified by DNA sequencing. This point mutation in the TATA box of UL42 was shown to confer BP5r by genetic experiments using a bacterial artificial chromosome (BAC) of HSV-1 strain KOS that I generated and characterized. Structure-activity relationships of BP5 were studied and a less cytotoxic analog, which retains considerable antiviral activity via the same mechanism, was identified. This new compound may be useful for selection of other resistant mutants.
520 $a MicroRNAs (miRNAs) are key regulators of gene expression in higher eukaryotes. To identify mIRNAs encoded by HSV-1, in collaboration with others, I validated and applied a computational method to screen the complete genome of HSV-1, and identified 11 HSV-1 genomic loci predicted to encode 13 miRNA precursors and 24 miRNA candidates. Eight of the HSV-1 miRNA candidates were predicted to be conserved in HSV-2. The precursor and the mature form of one HSV-1 miRNA candidate (HSV-1 miR-H1), which is encoded &sim;450 bp upstream of the transcription start site of the latency associated transcript, were detected during infection of Vero cells by Northern blot hybridization. These RNAs, which behave as late gene products, are not predicted to be conserved in HSV-2. I hypothesize that HSV-1 miRNAs regulate viral and host gene expression, have generated cell lines stably expressing HSV-1 miR-H1, and have constructed mutant HSV-1 not expressing miR-H1 using the KOS BAC.
590 $a School code: 0084.
650 4 $a Biology, Genetics. $3 1017730
650 4 $a Biology, Microbiology. $3 1017734
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Biology, Virology. $3 1019068
650 4 $a Health Sciences, Pharmacology. $3 1017717
690 $a 0307
690 $a 0369
690 $a 0410
690 $a 0419
690 $a 0720
710 2 $a Harvard University. $3 528741
773 0 $t Dissertation Abstracts International $g 68-02B.
790 $a 0084
790 1 0 $a Coen, Donald M., $e advisor
791 $a Ph.D.
792 $a 2007
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3251263