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Proteomic Analysis of HIV-1 Viral Co...

Santos, Steven.

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Proteomic Analysis of HIV-1 Viral Cores and the Identification of HIV-1 Replication Modulators.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Proteomic Analysis of HIV-1 Viral Cores and the Identification of HIV-1 Replication Modulators./
Author:	Santos, Steven.
Description:	145 p.
Notes:	Source: Dissertation Abstracts International, Volume: 76-06(E), Section: B.
Contained By:	Dissertation Abstracts International76-06B(E).
Subject:	Virology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3680028
ISBN:	9781321517866

Proteomic Analysis of HIV-1 Viral Cores and the Identification of HIV-1 Replication Modulators.
Santos, Steven.

Proteomic Analysis of HIV-1 Viral Cores and the Identification of HIV-1 Replication Modulators. - 145 p.

Source: Dissertation Abstracts International, Volume: 76-06(E), Section: B.

Thesis (Ph.D.)--The George Washington University, 2015.

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

During the course of HIV viral assembly and budding, an abundance of cellular proteins are incorporated into virus particles. The importance of these cellular proteins has become of great interest in recent years, with the discovery of multiple restriction factors, along with the fact that some cellular factors can modulate the early stages of HIV-1 replication. Many cellular proteins have been described previously via traditional biochemical methods and will be discussed in this dissertation. However, the functions of many other cellular factors incorporated into viruses have not been elucidated, such as whether or not these factors can affect the reverse transcription complex (RTC) and its eventual nuclear import. A mechanism that remains to be completely understood and identifying the cellular factors involved could assist with fully understanding how the reverse transcription complex is formed and imported into the nucleus.

ISBN: 9781321517866Subjects--Topical Terms:

642304
Virology.

Proteomic Analysis of HIV-1 Viral Cores and the Identification of HIV-1 Replication Modulators.
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100 1 $a Santos, Steven. $3 3181266
245 1 0 $a Proteomic Analysis of HIV-1 Viral Cores and the Identification of HIV-1 Replication Modulators.
300 $a 145 p.
500 $a Source: Dissertation Abstracts International, Volume: 76-06(E), Section: B.
500 $a Adviser: Michael Bukrinsky.
502 $a Thesis (Ph.D.)--The George Washington University, 2015.
506 $a This item must not be sold to any third party vendors.
520 $a During the course of HIV viral assembly and budding, an abundance of cellular proteins are incorporated into virus particles. The importance of these cellular proteins has become of great interest in recent years, with the discovery of multiple restriction factors, along with the fact that some cellular factors can modulate the early stages of HIV-1 replication. Many cellular proteins have been described previously via traditional biochemical methods and will be discussed in this dissertation. However, the functions of many other cellular factors incorporated into viruses have not been elucidated, such as whether or not these factors can affect the reverse transcription complex (RTC) and its eventual nuclear import. A mechanism that remains to be completely understood and identifying the cellular factors involved could assist with fully understanding how the reverse transcription complex is formed and imported into the nucleus.
520 $a In this dissertation, through the use of proteomics, we will describe how pure viral cores were isolated and their proteomes identified, in particular within viruses derived from monocytes, macrophages and T cells. Taking this a step further, to help shed some light on how cellular factors can affect the RTCs within an infected cell, we have identified two potential modulators of the HIV-1 life cycle, the first of which, MCM5 -- mini-chromosome maintenance complex component 5, was identified by observing cellular factors that were not randomly incorporated amongst differing cell types. Further analysis revealed that MCM5 binds to Gag, and that when MCM5 levels are manipulated in the producer cell reverse transcription is impaired, potentially through alteration of the RTC infrastructure. The second factor, inter-alpha-trypsin inhibitor isoform 4 (ITIH4) was identified within the viral cores of a unique cell clone that is non-permissive to HIV-1 infection, except in the presence of Vpr. This suggested that this might be the elusive cellular factor that Vpr is counteracting. Further analysis demonstrated that Vpr does indeed reduce ITIH4 expression and is inducible by interferon-alpha. Mechanistic analysis showed that ITIH4 works by dramatically decreasing HIV-1 protein expression. Preliminary evidence suggests that HIV transcription is targeted, potentially via transcription factors, but the exact mechanism remains to be determined and warrants further study.
590 $a School code: 0075.
650 4 $a Virology. $3 642304
650 4 $a Molecular biology. $3 517296
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710 2 $a The George Washington University. $b Microbiology and Emerging Infectious Diseases. $3 3181267
773 0 $t Dissertation Abstracts International $g 76-06B(E).
790 $a 0075
791 $a Ph.D.
792 $a 2015
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3680028