Harris, Katharine G
(2015)
Manipulation of host cell death and innate immune signaling pathways by Coxsackievirus B3.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Coxsackievirus B3 (CVB), an enterovirus, is a small, ssRNA virus with a genome of approximately 7 kB. There are 2 million symptomatic CVB infections annually in the United States, ranging from mild febrile illnesses to myocarditis, meningoencephalitis, or pancreatitis. CVB is a fecal-oral pathogen and must overcome diverse cellular barriers to cause disease, including the polarized epithelium lining the gastrointestinal tract. Viral infection of a host cell results in a variety of cellular responses that serve to control the viral infection. Once such response is the activation of intracellular innate immune signaling; this results in the production of type I interferon, which signals in an auto- and paracrine fashion to alter the transcriptional profile of a cell to inhibit viral replication. A second response to viral infection is the induction of cell death pathways; as viruses utilize host cell machinery for replication, early cell death of a host cell can result in an abortive infection. Here, I examine the ways in which CVB interfaces with these host cell pathways that affect viral replication. A primary mechanism utilized by CVB for altering host cell pathways is the production of the virally-encoded cysteine protease 3Cpro. 3Cpro is required to process the viral polypeptide but is also known to target cellular protein targets for proteolysis. Here, I identify two cellular proteins targeted for proteolysis by 3Cpro, Unc93b and RIP3, that are involved in the intracellular innate immune signaling and cell death pathways, respectively. I then characterize the roles of these proteins and their cleavage during CVB infection. In summary, I explore the ways in which CVB manipulates its host cell through proteolysis of host cell proteins by the virally-encoded protease 3Cpro and find that the balance between virus and host is finely tuned through the activity of this protease.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
11 May 2015 |
| Date Type: |
Publication |
| Defense Date: |
4 May 2015 |
| Approval Date: |
11 May 2015 |
| Submission Date: |
6 May 2015 |
| Access Restriction: |
1 year -- Restrict access to University of Pittsburgh for a period of 1 year. |
| Number of Pages: |
151 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Molecular Virology and Microbiology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Virology
Innate Immunology
Necroptosis
Toll-like receptor signaling
Coxsackievirus B3
Enterovirus |
| Date Deposited: |
11 May 2015 12:54 |
| Last Modified: |
15 Nov 2016 14:28 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/25156 |
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