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Multiple nuclear receptors and circa...

Hwang, Jesse.

Multiple nuclear receptors and circadian rhythm factors modulate human cytomegalovirus replication.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Multiple nuclear receptors and circadian rhythm factors modulate human cytomegalovirus replication.
Author:	Hwang, Jesse.
Description:	218 p.
Notes:	Source: Dissertation Abstracts International, Volume: 75-03(E), Section: B.
Notes:	Adviser: Thomas E. Shenk.
Contained By:	Dissertation Abstracts International75-03B(E).
Subject:	Molecular biology.
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3604477
ISBN:	9781303602016

Multiple nuclear receptors and circadian rhythm factors modulate human cytomegalovirus replication.
Hwang, Jesse.

Multiple nuclear receptors and circadian rhythm factors modulate human cytomegalovirus replication. - 218 p.

Source: Dissertation Abstracts International, Volume: 75-03(E), Section: B.

Thesis (Ph.D.)--Princeton University, 2013.

This item must not be sold to any third party vendors.

Human cytomegalovirus (HCMV) infection is prevalent worldwide. Although most infected people remain asymptomatic, immunocompromised individuals or neonates remain susceptible to morbidity. The molecular mechanisms governing viral replication have been studied for decades, yet the understanding remains incomplete. Further illumination of the viral life cycle will open up possibilities to develop novel anti-viral therapeutics and gain insight into the evolutionary history of the virus.

ISBN: 9781303602016Subjects--Topical Terms:

188737
Molecular biology.

Multiple nuclear receptors and circadian rhythm factors modulate human cytomegalovirus replication.
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245 1 0 $a Multiple nuclear receptors and circadian rhythm factors modulate human cytomegalovirus replication.
300 $a 218 p.
500 $a Source: Dissertation Abstracts International, Volume: 75-03(E), Section: B.
500 $a Adviser: Thomas E. Shenk.
502 $a Thesis (Ph.D.)--Princeton University, 2013.
506 $a This item must not be sold to any third party vendors.
506 $a This item must not be added to any third party search indexes.
520 $a Human cytomegalovirus (HCMV) infection is prevalent worldwide. Although most infected people remain asymptomatic, immunocompromised individuals or neonates remain susceptible to morbidity. The molecular mechanisms governing viral replication have been studied for decades, yet the understanding remains incomplete. Further illumination of the viral life cycle will open up possibilities to develop novel anti-viral therapeutics and gain insight into the evolutionary history of the virus.
520 $a One area in "cytomegalovirology" that has not been explored in depth is the interaction of the virus with the nuclear receptor superfamily. A highly-conserved and ancient family of transcription factors, each member has a unique set of biological functions. Many bind to and sense hydrophobic ligands, transmitting signals for optimal physiological output. Some are constitutively active and act independently of ligand. Of the 48 nuclear receptor genes in the human genome, only a subset had been studied previously in the context of HCMV infection. I have broadened these earlier studies by carrying out a shRNA screen against all 48 nuclear receptors. Among the putative hits, estrogen-related receptor &agr; (ERR&agr;) was further validated to be important for viral replication. Knockdown with multiple shRNAs or pharmacological inhibition of ERR&agr; suppressed HCMV infectious yield. This ligand-independent nuclear receptor regulated the metabolism of infected cells, the production of at least a portion of HCMV immediate early proteins, and viral DNA replication.
520 $a The circadian rhythm is present in almost all life forms, from archaea to bacteria to eukarya. The ability to respond to time-dependent external and internal cues allows for optimal fitness, and the molecular details of how organisms sense and respond to these signals continue to be revealed. However, few studies have investigated this important process during viral infection. I have examined how HCMV alters the core machinery of the circadian clock and determined that the core transcriptional-translational loop is not required for viral replication. BMAL1, a transcription factor that plays a central role in circadian regulation, is highly induced at the protein level following infection, but its accumulation antagonizes HCMV replication. In addition, I show that another circadian transcription factor, the nuclear receptor Rev-erb&agr;, can be targeted by a ligand to reduce viral replication.
520 $a In the final chapters, I investigated the role of NAD metabolism during HCMV infection and showed that the NAD salvage pathway is a druggable target to impede successful progeny production. In addition, the potential role of eIF-5A hypusination will be discussed, followed by demonstration of unique cell biological features of HCMV-infected cells.
590 $a School code: 0181.
650 4 $a Molecular biology. $3 188737
650 4 $a Virology. $3 196498
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710 2 $a Princeton University. $b Molecular Biology. $3 708628
773 0 $t Dissertation Abstracts International $g 75-03B(E).
790 $a 0181
791 $a Ph.D.
792 $a 2013
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3604477