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Investigating the ubiquitin-proteasome system for targeted reversal of HIV-1 latency

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TitleInfo
Title
Investigating the ubiquitin-proteasome system for targeted reversal of HIV-1 latency
Name (type = personal)
NamePart (type = family)
Russnak
NamePart (type = given)
Timothy
NamePart (type = date)
1986-
DisplayForm
Timothy Russnak
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Gelinas
NamePart (type = given)
Celine
DisplayForm
Celine Gelinas
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Walworth
NamePart (type = given)
Nancy
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Nancy Walworth
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Roth
NamePart (type = given)
Monica
DisplayForm
Monica Roth
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Fan
NamePart (type = given)
Huizhou
DisplayForm
Huizhou Fan
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
School of Graduate Studies
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (qualifier = exact)
2018
DateOther (qualifier = exact); (type = degree)
2018-01
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2018
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
HIV is a worldwide epidemic, remaining the ever-present specter among all matters regarding blood or other bodily fluids, such as sexual intercourse, healthcare, blood transfusions, or even surgery, particularly in resource-poor areas. While antiretroviral drug therapy is highly successful in suppressing the virus and preventing transmission, it cannot cure the infection due to latency – the ability of HIV to go into a silent state within cells; once drug therapy is stopped, reactivating latent virus will cause a surge of the viral load within days or weeks. Current drug therapies do not act on this latent reservoir, necessitating lifelong adherence to medication, which is both extremely costly and comes with negative side effects. The mainstay of research into HIV latency deals with teasing apart the mechanisms involved in establishing and maintaining latency, in the hopes of finding drug compounds which can efficiently reverse latency and thus purge the body of hidden HIV. In searching for cellular pathways involved in latency, our lab has employed a genome-wide negative-selection screen, which indicated that the ubiquitin-proteasome system plays a role in maintaining latency. This led us to discover that proteasome inhibitors act as bifunctional antagonists of HIV, both reversing the latent state and reducing infectivity of virions. We went on to identify the specific ubiquitin-proteasome pathway that is involved in maintaining latency. We then investigated the activity of a small-molecule inhibitor of one component of the ubiquitin-proteasome system, showing its ability to reactivate latent HIV in both a primary cell model and in cells taken from aviremic HIV+ patients. These results are a proof-of-concept that inhibition of a specific ubiquitin-proteasome pathway can allow for specific reversal of HIV latency.
Subject (authority = RUETD)
Topic
Microbiology and Molecular Genetics
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_8536
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xi, 168 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Subject (authority = ETD-LCSH)
Topic
HIV infections--Treatment
Note (type = statement of responsibility)
by Timothy Russnak
RelatedItem (type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Location
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NjNbRU
Identifier (type = doi)
doi:10.7282/T3TF01JM
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Russnak
GivenName
Timothy
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2017-11-14 15:49:47
AssociatedEntity
Name
Timothy Russnak
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
RightsEvent
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2018-01-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2020-01-31
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after January 31st, 2020.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical

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2018-01-02T17:10:22
DateCreated (point = end); (encoding = w3cdtf); (qualifier = exact)
2018-01-02T17:10:22
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