Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Manipulation of host cell death and innate immune signaling pathways by Coxsackievirus B3

Harris, Katharine G (2015) Manipulation of host cell death and innate immune signaling pathways by Coxsackievirus B3. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

Primary Text

Download (3MB)


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.


Social Networking:
Share |


Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Harris, Katharine Gkatharine.g.harris@gmail.com0000-0001-6141-1207
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairCoyne, Carolyn Bcoynec2@pitt.eduCOYNEC2
Committee MemberBomberger, Jennifer M.jbomb@pitt.eduJBOMB
Committee MemberGaffen, Sarah Lsig65@pitt.eduSIG65
Committee MemberSarkar , Saumendrasaumen@pitt.eduSAUMEN
Committee MemberYu, Jianyuj2@pitt.eduYUJ2
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


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item