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Defining the roles of human papillom...

DiGiuseppe, Stephen Andrew.

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Defining the roles of human papillomavirus capsid proteins following the later trafficking events of the entry process.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Defining the roles of human papillomavirus capsid proteins following the later trafficking events of the entry process./
Author:	DiGiuseppe, Stephen Andrew.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2017,
Description:	302 p.
Notes:	Source: Dissertation Abstracts International, Volume: 78-07(E), Section: B.
Contained By:	Dissertation Abstracts International78-07B(E).
Subject:	Virology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10586304
ISBN:	9781369657197

Defining the roles of human papillomavirus capsid proteins following the later trafficking events of the entry process.
DiGiuseppe, Stephen Andrew.

Defining the roles of human papillomavirus capsid proteins following the later trafficking events of the entry process. - Ann Arbor : ProQuest Dissertations & Theses, 2017 - 302 p.

Source: Dissertation Abstracts International, Volume: 78-07(E), Section: B.

Thesis (Ph.D.)--Louisiana State University Health Sciences Center - Shreveport, 2017.

Human papillomavirus (HPV) are non-enveloped DNA tumor viruses that infect mucosal or epithelial cells. While most infections are benign, infections by the high-risk types are associated with increased risk of cancers and cause approximately five percent of all cancers worldwide. HPV infections will continue to be a health burden in the future mainly due to low vaccination rates. Therefore, there is a continued interest in studying the mechanisms of how HPV can establish an infection.

ISBN: 9781369657197Subjects--Topical Terms:

642304
Virology.

Defining the roles of human papillomavirus capsid proteins following the later trafficking events of the entry process.
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245 1 0 $a Defining the roles of human papillomavirus capsid proteins following the later trafficking events of the entry process.
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300 $a 302 p.
500 $a Source: Dissertation Abstracts International, Volume: 78-07(E), Section: B.
502 $a Thesis (Ph.D.)--Louisiana State University Health Sciences Center - Shreveport, 2017.
520 $a Human papillomavirus (HPV) are non-enveloped DNA tumor viruses that infect mucosal or epithelial cells. While most infections are benign, infections by the high-risk types are associated with increased risk of cancers and cause approximately five percent of all cancers worldwide. HPV infections will continue to be a health burden in the future mainly due to low vaccination rates. Therefore, there is a continued interest in studying the mechanisms of how HPV can establish an infection.
520 $a The HPV capsid is composed of two viral proteins, 1.1 and L2. After binding and internalization, the virion uncoats within acidified endosomes. The viral proteins undergo conformational changes, which result in the viral genome trafficking from the endosomes to the trans-Golgi network (TGN). Following nuclear envelope breakdown during mitosis, the viral genome is delivered to the nucleus. Currently, the question of how the viral genome traffics to the nucleus during this time is almost completely unexplored.
520 $a Herein, we demonstrate that after uncoating, L1 and L2 proteins undergo important conformational changes. While most of the L1 dissocirates, some L1 capsomeres remain associated with L2 and the viral genome to likely stabilize the complex. We hypothesize that the release of adjacent 1.1 capsomeres liberates the hydrophobic C-terminal arm of L2, which penetrates intracellular membranes to engage the cytosolic factors necessary to facilitate trafficking to the TGN. Following the onset of mitosis, the viral genome dissociates from the TGN and lines up along microtubules. During this time, the viral genome remains protected in a membrane-bound vesicle while being delivered to the nucleus and isn't released until after the nuclear envelope has reformed. Finally, the viral genome associates with PML nuclear bodies and initiates the viral transcription program to establish the infection. Taken together, our findings provide further insight into to the less understood later events of HPV entry process. These studies are not just important for the field of HPV research, but also understanding viral strategies for safely delivering the viral genome to the nucleus to initiate infections.
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