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Noncytotoxic Lytic Granule-Mediated Maintenance of HSV-1 Neuronal Latency

Knickelbein, Jared Evan (2008) Noncytotoxic Lytic Granule-Mediated Maintenance of HSV-1 Neuronal Latency. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Reactivation of herpes simplex virus (HSV) from neuronal latency is a common and potentially devastating cause of disease worldwide. CD8 T cells can completely inhibit HSV reactivation, and IFN-gamma affords a portion of this protection. We now show that CD8 T cell lytic granules are also required for the maintenance of HSV type 1 (HSV-1) neuronal latency both in vivo and in ex vivo cultures, and that their directed release into junctions with neurons in latently infected ganglia does not induce neuronal apoptosis. Our findings support a non-lethal mechanism of viral inactivation by demonstrating that the lytic granule component, granzyme B, degrades the HSV-1 immediate early protein, ICP4, which is essential for further viral gene expression. These findings reveal a novel non-apoptotic function of granzyme B in the context of inhibiting viral reactivation from latency.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Knickelbein, Jared Evanjek33@pitt.eduJEK33
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairHendricks, Robert Lhendricksrr@upmc.eduRLH13
Committee MemberFlynn, Joanne Ljoanne@pitt.eduJOANNE
Committee MemberMcKenna, Kyle
Committee MemberSalter, Russell Drds@pitt.eduRDS
Committee MemberWatkins, Simon Cswatkins@pitt.eduSWATKINS
Date: 10 September 2008
Date Type: Completion
Defense Date: 25 August 2008
Approval Date: 10 September 2008
Submission Date: 8 September 2008
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Immunology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: CD8 T cells; Granzymes; Herpes simplex virus type 1
Other ID:, etd-09082008-100630
Date Deposited: 10 Nov 2011 20:01
Last Modified: 19 Dec 2016 14:37


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