Repository logo
 

The role of cellular RNA decay pathways in Sindbis virus infection

Simple item page
dc.contributor.authorGarneau, Nicole L., author
dc.contributor.authorWilusz, Jeffrey, advisor
dc.contributor.authorWilusz, Carol, advisor
dc.date.accessioned2024-03-13T19:53:47Z
dc.date.available2024-03-13T19:53:47Z
dc.date.issued2009
dc.description.abstractSindbis virus is the prototypic species of the Alphavirus genus. Members of this genus can cause febrile illness, arthritic pain and potentially fatal encephalitis. The alphaviral lifecycle generates single-stranded, positive-sense genomic and subgenomic RNAs which are capped on the 5' terminus, contain 5' and 3' untranslated regions (UTRs), and are polyadenylated at the 3' terminus. These characteristics make alphaviral RNAs similar in structure to cellular mRNAs. Such features allow alphaviruses, such as Sindbis, to benefit from the host cell translation process; however, they also could make the viral transcript vulnerable to the cellular mRNA decay enzymes. mRNA decay is a form of post-transcriptional regulation of gene expression found in both mammalian and mosquito hosts of Sindbis virus. The interaction between Sindbis viral RNAs and mRNA decay pathways was investigated in this dissertation. Using a novel in vivo viral RNA decay assay to accurately assess the rate of alphavirus RNA decay during infection, we found a correlation between Sindbis viral RNA stability and viral replication efficiency, demonstrating mRNA decay potentially represents a novel host cell restriction factor. We established that the RNAi pathway likely plays a dominant role in the decay of the viral RNAs during infection in mammalian cells. These data represent a novel demonstration that the RNAi pathway is potentially an effective antiviral response in the mammalian host as it is in the mosquito host. With the development of a highly sensitive method to assess poly(A) tail length, we were able to demonstrate the importance of the viral 3'UTR as a repressor of deadenylation of viral RNAs in vivo. Lastly, we found that Repeat Sequence Element 3 (RSE 3), the third and final in a series of three RSEs within the viral 3'UTR, hinders the processivity of the cellular deadenylases on viral RNAs in vitro, providing the first evidence for a function of this conserved alphaviral genome element. Taken together, these results shed light on the much understudied area of viral RNA decay. Our data support the notion that the interaction between viral RNAs and the cellular RNA decay machinery is very important to the biology of the virus.
dc.format.mediumborn digital
dc.format.mediumdoctoral dissertations
dc.identifierETDF_Garneau_2009_3374648.pdf
dc.identifier.urihttps://hdl.handle.net/10217/237746
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2000-2019
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.rights.licensePer the terms of a contractual agreement, all use of this item is limited to the non-commercial use of Colorado State University and its authorized users.
dc.subjectalphavirus
dc.subjectRNA decay
dc.subjectRNAi
dc.subjectSindbis virus
dc.subjectmolecular biology
dc.subjectvirology
dc.titleThe role of cellular RNA decay pathways in Sindbis virus infection
dc.typeText
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineMicrobiology, Immunology, and Pathology
thesis.degree.grantorColorado State University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D.)

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
ETDF_Garneau_2009_3374648.pdf
Size:
6.36 MB
Format:
Adobe Portable Document Format
Download

Collections

2000-2019
Theses and Dissertations