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Regulation of HSV gene expression: ...

McNamee, Elizabeth Emily.

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Regulation of HSV gene expression: Two viral functions implicated in the stimulation of late gene transcription.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Regulation of HSV gene expression: Two viral functions implicated in the stimulation of late gene transcription./
Author:	McNamee, Elizabeth Emily.
Description:	176 p.
Notes:	Adviser: David M. Knipe.
Contained By:	Dissertation Abstracts International63-04B.
Subject:	Biology, Microbiology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3051242
ISBN:	0493657746

Regulation of HSV gene expression: Two viral functions implicated in the stimulation of late gene transcription.
McNamee, Elizabeth Emily.

Regulation of HSV gene expression: Two viral functions implicated in the stimulation of late gene transcription. - 176 p.

Adviser: David M. Knipe.

Thesis (Ph.D.)--Harvard University, 2002.

Herpes simplex virus, like many DNA viruses, regulates the transcription of its genes in a temporal manner. The cis-acting effect of viral DNA replication and the viral proteins ICP4, ICP27 and ICP8 are all required for transcription of the late genes and synthesis of high levels of late, mostly structural, proteins. ICP8 and ICP27 also play essential roles in viral DNA replication, but their effects on replication have been separated genetically from their effects on late gene transcription with mutant versions of the proteins that support wildtype DNA replication, but are defective for late gene expression. Here, I initially describe a correlation between the formation of large replication compartments and late gene expression. To do this, I utilized a dominant negative ICP8 mutant that confers a specific inhibition of late gene transcription. I discovered that in the presence of <italic>d</italic>105 ICP8, most cells did not form replication compartments. The lack of replication compartment formation correlated with a lack of gene expression in those cells. I proposed a model of action for <italic>d</italic>105 ICP8 where it prevented normal ICP8 localization to progeny DNA, and thus also prevented normal replication compartment maturation, which includes the activation of late gene transcription. I then performed a yeast two-hybrid screen designed to identify cellular proteins that interact with ICP8, specifically with the region of ICP8 deleted in the <italic> d</italic>105 mutation. I identified several potential interactors, and proceeded to attempt to confirm the interaction between one of them, p32, and ICP8, in vivo. Additionally, I identified ICP27 as a protein co-immunoprecipitating with ICP8 from infected cell lysates. I identified an ICP27 mutant that did not co-precipitate with ICP8. This mutation in ICP27 is specifically defective for stimulation of late gene expression, thus implicating the interaction between ICP8 and ICP27 in the regulation of late gene expression. This is the first study to definitively link ICP8 and ICP27 in the regulation of late gene expression. The interaction between ICP8 and ICP27 is now implicated in the regulatory pathway that leads to successful late gene expression, and supports previous evidence indicating that both proteins are involved in transcriptional, as opposed to post-transcriptional, processes.

ISBN: 0493657746Subjects--Topical Terms:

1017734
Biology, Microbiology.

Regulation of HSV gene expression: Two viral functions implicated in the stimulation of late gene transcription.
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035 $a (UnM)AAI3051242
035 $a AAI3051242
040 $a UnM $c UnM
100 1 $a McNamee, Elizabeth Emily. $3 1251324
245 1 0 $a Regulation of HSV gene expression: Two viral functions implicated in the stimulation of late gene transcription.
300 $a 176 p.
500 $a Adviser: David M. Knipe.
500 $a Source: Dissertation Abstracts International, Volume: 63-04, Section: B, page: 1684.
502 $a Thesis (Ph.D.)--Harvard University, 2002.
520 $a Herpes simplex virus, like many DNA viruses, regulates the transcription of its genes in a temporal manner. The cis-acting effect of viral DNA replication and the viral proteins ICP4, ICP27 and ICP8 are all required for transcription of the late genes and synthesis of high levels of late, mostly structural, proteins. ICP8 and ICP27 also play essential roles in viral DNA replication, but their effects on replication have been separated genetically from their effects on late gene transcription with mutant versions of the proteins that support wildtype DNA replication, but are defective for late gene expression. Here, I initially describe a correlation between the formation of large replication compartments and late gene expression. To do this, I utilized a dominant negative ICP8 mutant that confers a specific inhibition of late gene transcription. I discovered that in the presence of <italic>d</italic>105 ICP8, most cells did not form replication compartments. The lack of replication compartment formation correlated with a lack of gene expression in those cells. I proposed a model of action for <italic>d</italic>105 ICP8 where it prevented normal ICP8 localization to progeny DNA, and thus also prevented normal replication compartment maturation, which includes the activation of late gene transcription. I then performed a yeast two-hybrid screen designed to identify cellular proteins that interact with ICP8, specifically with the region of ICP8 deleted in the <italic> d</italic>105 mutation. I identified several potential interactors, and proceeded to attempt to confirm the interaction between one of them, p32, and ICP8, in vivo. Additionally, I identified ICP27 as a protein co-immunoprecipitating with ICP8 from infected cell lysates. I identified an ICP27 mutant that did not co-precipitate with ICP8. This mutation in ICP27 is specifically defective for stimulation of late gene expression, thus implicating the interaction between ICP8 and ICP27 in the regulation of late gene expression. This is the first study to definitively link ICP8 and ICP27 in the regulation of late gene expression. The interaction between ICP8 and ICP27 is now implicated in the regulatory pathway that leads to successful late gene expression, and supports previous evidence indicating that both proteins are involved in transcriptional, as opposed to post-transcriptional, processes.
590 $a School code: 0084.
650 4 $a Biology, Microbiology. $3 1017734
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710 2 0 $a Harvard University. $3 528741
773 0 $t Dissertation Abstracts International $g 63-04B.
790 $a 0084
790 1 0 $a Knipe, David M., $e advisor
791 $a Ph.D.
792 $a 2002
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3051242