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Host cellular cholesterol distribution and dynamics during enteroviral infection
Descriptive
TitleInfo
Title
Host cellular cholesterol distribution and dynamics during enteroviral infection
Name
(type = personal)
NamePart
(type = family)
Santiana
NamePart
(type = given)
Marianita
NamePart
(type = date)
1973-
DisplayForm
Marianita Santiana
Role
RoleTerm
(authority = RULIB)
author
Name
(type = personal)
NamePart
(type = family)
Altan-Bonnet
NamePart
(type = given)
Nihal
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Nihal Altan-Bonnet
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
chair
Name
(type = personal)
NamePart
(type = family)
Cali
NamePart
(type = given)
Ann
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Ann Cali
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Tran
NamePart
(type = given)
Tracy
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Tracy Tran
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Gao
NamePart
(type = given)
Nan
DisplayForm
Nan Gao
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Donaldson
NamePart
(type = given)
Julie
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Julie Donaldson
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
outside member
Name
(type = corporate)
NamePart
Rutgers University
Role
RoleTerm
(authority = RULIB)
degree grantor
Name
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NamePart
Graduate School - Newark
Role
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school
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Text
Genre
(authority = marcgt)
theses
OriginInfo
DateCreated
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2015
DateOther
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(type = degree)
2015-05
CopyrightDate
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(qualifier = exact)
2015
Place
PlaceTerm
(type = code)
xx
Language
LanguageTerm
(authority = ISO639-2b);
(type = code)
eng
Abstract
(type = abstract)
Many RNA viruses, including enteroviruses, remodel host ER membranes to form platforms with unique lipid components to assemble replication complexes and synthesize new viral RNA. Cholesterol is a critical component of cellular membranes regulating fluidity and being indispensable for proper assembly and function of membrane based protein-lipid complexes. Here we show that enteroviruses harness the clathrin mediated endocytosis (CME) pathway to transfer free cholesterol from the plasma membrane to the viral replication organelles (VROs). We show that cholesterol is responsible for regulating viral protein processing and facilitates viral RNA synthesis, and disrupting CME causes cellular cholesterol pools to be stored in lipid droplets obstructing the transfer to VROs and inhibiting viral replication. In contrast, we found that the presence of excess intracellular cholesterol, as in cells lacking caveolins or those from patients with Niemann-Pick disease, stimulates viral replication. We demonstrate that, the redistribution of free cellular cholesterol and the cellular recycle dynamics are affected during infection. The CME rate of uptake does not change during the initial 2 hours of infection while the rate of cellular endosomal recycling is inhibited resulting in a net decrease of free cholesterol at the plasma membrane, and facilitating the access and active transfer of cholesterol from enriched internal cellular compartments to VROs. Our findings indicate that cholesterol is critical for enteroviral replication and that CME has an important role in the enteroviral life cycle and in the host cellular cholesterol homeostasis.
Subject
(authority = RUETD)
Topic
Biology
Subject
(authority = ETD-LCSH)
Topic
Endocytosis
RelatedItem
(type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
(type = RULIB)
ETD
Identifier
ETD_6216
PhysicalDescription
Form
(authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xiv, 125 p. : ill.)
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Subject
(authority = ETD-LCSH)
Topic
Enteroviruses
Note
(type = statement of responsibility)
by Marianita Santiana
RelatedItem
(type = host)
TitleInfo
Title
Graduate School - Newark Electronic Theses and Dissertations
Identifier
(type = local)
rucore10002600001
Location
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(authority = marcorg);
(displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier
(type = doi)
doi:10.7282/T351414Q
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
Santiana
GivenName
Marianita
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
(encoding = w3cdtf);
(qualifier = exact);
(point = start)
2015-03-18 13:21:37
AssociatedEntity
Name
Marianita Santiana
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - Newark
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)
2015-05-31
DateTime
(encoding = w3cdtf);
(qualifier = exact);
(point = end)
2017-05-30
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after May 30th, 2017.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical
RULTechMD
(ID = TECHNICAL1)
ContentModel
ETD
OperatingSystem
(VERSION = 5.1)
windows xp
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Statistical Profile