Fox, Hannah
(2019)
The Role of HSV-1 Protein ICP22 in Transcription.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
This is the latest version of this item.
Abstract
Herpes Simplex Virus type 1 (HSV-1) productively replicates in epithelial cells before establishing a life-long infection in sensory neurons. During productive infection, HSV-1 alters cellular processes and hijacks many cellular proteins to aid in viral replication. Viral gene transcription requires cellular RNA polymerase II (RNA pol II) and is highly regulated. The viral Immediate Early (IE) proteins ICP4, ICP0, ICP27, and ICP22 have all been recognized to play roles in regulating viral transcription. To clarify the role of ICP22 in transcription regulation, we defined its interactions with cellular transcription factors and its effects on both viral and cellular gene transcription. We determined that: i) the FACT complex, a cellular transcription elongation factor, did not associate with viral DNA in the absence of ICP22; ii) in the absence of ICP22, viral transcription decreases and RNA pol II does not efficiently proceed from viral promoters to gene bodies; iii) ICP22 directly interacts with the FACT complex and other cellular factors involved in transcription; and iv) ICP22 is required for the efficient repression of cellular gene transcription.
Our studies suggest a role for ICP22 in regulating transcription in cells infected with HSV-1. We propose that ICP22 recruits cellular factors necessary for efficient transcript elongation to viral genomes. Furthermore, the ability of ICP22 to recruit these factors supports a mechanism through which HSV-1 limits cellular transcription while encouraging robust viral transcription. ICP22 is therefore integral to the efficient production of infectious virus and the sustained evasion of host immune responses.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
| Title | Member | Email Address | Pitt Username | ORCID |
|---|
| Committee Chair | DeLuca, Neal | ndeluca@pitt.edu | | |
|
| Date: |
28 January 2019 |
| Date Type: |
Publication |
| Defense Date: |
2 November 2018 |
| Approval Date: |
28 January 2019 |
| Submission Date: |
13 December 2018 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
142 |
| 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: |
ICP22, HSV-1, Viral Transcription Regulation |
| Date Deposited: |
28 Jan 2019 18:00 |
| Last Modified: |
28 Jan 2019 18:00 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/35934 |
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