Possible Role for Adaptor Protein Complexes in Sorting of Human Papillomavirus

Persistent Link:
http://hdl.handle.net/10150/297737
Title:
Possible Role for Adaptor Protein Complexes in Sorting of Human Papillomavirus
Author:
Schlegel, Angela Marie
Issue Date:
2013
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Human papillomaviruses (HPVs) are non-enveloped DNA viruses that infect genital and mucosal epithelium and include strains carrying different levels of risk for the host upon infection, including potentially oncogenic high-risk strains. HPVs consist of a ~8 kb circular dsDNA genome encapsidated by two structural proteins: the major capsid protein L1 and the minor capsid protein L2. The pathway HPV uses to infect cells is not well understood; in particular many of the host cell factors that HPV requires for a successful infection have not been identified. Previous work indicates that L2 interacts with members of the adaptor protein (AP) protein complex family, which aid in the vesicular sorting and trafficking of endocytosed cargo. The goal of this project is to determine which AP complexes L2 interacts with, how these interactions occur, and the functions of these interactions during infection. L2 contains multiple YxxΦ sorting signals, with varying degrees of conservation among HPV types. Yeast two-hybrid screens indicate that full-length L2 interacts with all isoforms of complexes AP-1 through AP-4 and that smaller L2 peptides, each containing single YxxΦ sorting signals, interact with fewer AP complexes. siRNA single knockdowns of each AP complex show varying effects on infectivity, with knockdown of μ1A having the largest effect. Infections with viruses containing mutations of these L2 sorting signals show decreased infectivity, strongly supporting a role of AP complexes in infection. These experiments also indicate that not all YXXΦ motifs within L2 are involved in these interactions and some may be important for proper L2 folding and structure. Current work seeks to determine causes of these defects in infectivity and determine trafficking phenotypes of those mutant viruses to assess specific roles for L2-AP complex interactions.
Type:
text; Electronic Thesis
Degree Name:
B.S.
Degree Level:
bachelors
Degree Program:
Honors College; Biochemistry
Degree Grantor:
University of Arizona
Advisor:
Campos, Samuel K.; Tsao, Tsu-Shuen

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titlePossible Role for Adaptor Protein Complexes in Sorting of Human Papillomavirusen_US
dc.creatorSchlegel, Angela Marieen_US
dc.contributor.authorSchlegel, Angela Marieen_US
dc.date.issued2013-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractHuman papillomaviruses (HPVs) are non-enveloped DNA viruses that infect genital and mucosal epithelium and include strains carrying different levels of risk for the host upon infection, including potentially oncogenic high-risk strains. HPVs consist of a ~8 kb circular dsDNA genome encapsidated by two structural proteins: the major capsid protein L1 and the minor capsid protein L2. The pathway HPV uses to infect cells is not well understood; in particular many of the host cell factors that HPV requires for a successful infection have not been identified. Previous work indicates that L2 interacts with members of the adaptor protein (AP) protein complex family, which aid in the vesicular sorting and trafficking of endocytosed cargo. The goal of this project is to determine which AP complexes L2 interacts with, how these interactions occur, and the functions of these interactions during infection. L2 contains multiple YxxΦ sorting signals, with varying degrees of conservation among HPV types. Yeast two-hybrid screens indicate that full-length L2 interacts with all isoforms of complexes AP-1 through AP-4 and that smaller L2 peptides, each containing single YxxΦ sorting signals, interact with fewer AP complexes. siRNA single knockdowns of each AP complex show varying effects on infectivity, with knockdown of μ1A having the largest effect. Infections with viruses containing mutations of these L2 sorting signals show decreased infectivity, strongly supporting a role of AP complexes in infection. These experiments also indicate that not all YXXΦ motifs within L2 are involved in these interactions and some may be important for proper L2 folding and structure. Current work seeks to determine causes of these defects in infectivity and determine trafficking phenotypes of those mutant viruses to assess specific roles for L2-AP complex interactions.en_US
dc.typetexten_US
dc.typeElectronic Thesisen_US
thesis.degree.nameB.S.en_US
thesis.degree.levelbachelorsen_US
thesis.degree.disciplineHonors Collegeen_US
thesis.degree.disciplineBiochemistryen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorCampos, Samuel K.-
dc.contributor.advisorTsao, Tsu-Shuen-
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