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Identification of small molecule inh...

Wong, Scott William.

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Identification of small molecule inhibitors of simian immunodeficiency virus Nef-mediated enhancement of virus replication.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Identification of small molecule inhibitors of simian immunodeficiency virus Nef-mediated enhancement of virus replication./
Author:	Wong, Scott William.
Description:	229 p.
Notes:	Source: Dissertation Abstracts International, Volume: 68-09, Section: B, page: 5786.
Contained By:	Dissertation Abstracts International68-09B.
Subject:	Biology, Bioinformatics. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3283054
ISBN:	9780549255475

Identification of small molecule inhibitors of simian immunodeficiency virus Nef-mediated enhancement of virus replication.
Wong, Scott William.

Identification of small molecule inhibitors of simian immunodeficiency virus Nef-mediated enhancement of virus replication. - 229 p.

Source: Dissertation Abstracts International, Volume: 68-09, Section: B, page: 5786.

Thesis (Ph.D.)--University of California, Davis, 2007.

Nef, a viral protein encoded by the simian immunodeficiency virus (SIV) and the human immunodeficiency virus (HIV) is important for pathogenesis in rhesus macaques and humans and virus replication in unstimulated peripheral blood mononuclear cells (PBMCs). This dissertation contributes towards understanding Nef's importance in vivo using in vitro analysis.

ISBN: 9780549255475Subjects--Topical Terms:

1018415
Biology, Bioinformatics.

Identification of small molecule inhibitors of simian immunodeficiency virus Nef-mediated enhancement of virus replication.
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020 $a 9780549255475
035 $a (UMI)AAI3283054
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100 1 $a Wong, Scott William. $3 1271179
245 1 0 $a Identification of small molecule inhibitors of simian immunodeficiency virus Nef-mediated enhancement of virus replication.
300 $a 229 p.
500 $a Source: Dissertation Abstracts International, Volume: 68-09, Section: B, page: 5786.
502 $a Thesis (Ph.D.)--University of California, Davis, 2007.
520 $a Nef, a viral protein encoded by the simian immunodeficiency virus (SIV) and the human immunodeficiency virus (HIV) is important for pathogenesis in rhesus macaques and humans and virus replication in unstimulated peripheral blood mononuclear cells (PBMCs). This dissertation contributes towards understanding Nef's importance in vivo using in vitro analysis.
520 $a A novel kinase activity was associated with CD8-SIV Nef, designated SIV Nef N-terminal kinase (STNK), phosphorylated a 49kDa protein in an in vitro kinase assay. In this study, the N-terminal domain that conferred SNTK activity was shown to begin at residue 14 of SIV Nef. Tyrosine residues at positions 28, 60 and 65 were crucial for SNTK activity. When mutated to alanines, these mutant proteins lacked SNTK activity.
520 $a The major emphasis of this research is to further study Nef's effect on SIV. Small molecule compounds that bind SIV Nef were identified that inhibit virus replication. Recombinant SIV Nef protein was used to screen one-bead one-compound combinatorial small molecule libraries to identify ligands that bind Nef. After screening &sim;410,000 compounds from four different libraries, several small molecules were identified binding to SIV Nef.
520 $a Small molecule compounds were tested for their effects on SIV replication in unstimulated rhesus macaque PBMCs. Nine candidate molecules inhibited SIV replication. Two compounds, 01SMB9 and SW211, lowered SIV replication in unstimulated PBMCs better than other candidate molecules. These compounds also inhibited HIV replication in unstimulated human PBMCs, although with lower potency.
520 $a To identify a potential mechanisms of inhibition, these two compounds were examined for their effects on Nef's in vitro functions. In a cell line that measured the infectivity of a single-cycle virus infection, only 01SMB9, but not SW211 lowered virus infectivity. However, SW211 inhibited Nef-mediated p21-activated kinase (PAK) activation while 01SMB9 did not. Neither compound altered Nef-mediated downregulation of CD4 or MHC-I from the cell surface. These results represent a proof of principle for the design of novel anti-viral agents targeting Nef. Compounds identified in these studies will represent a new class of HIV inhibitors.
590 $a School code: 0029.
650 4 $a Biology, Bioinformatics. $3 1018415
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Biology, Virology. $3 1019068
690 $a 0307
690 $a 0715
690 $a 0720
710 2 $a University of California, Davis. $3 1018682
773 0 $t Dissertation Abstracts International $g 68-09B.
790 $a 0029
791 $a Ph.D.
792 $a 2007
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3283054