Dremel, Sarah
(2020)
HSV-1 reprogramming of the host transcriptional environment.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Herpes Simplex Virus-1 (HSV-1) is a ubiquitous pathogen of the oral and genital mucosa. The 152 kilobase double stranded DNA virus employs a coordinated cascade of transcriptional events to efficiently generate progeny. Using Next Generation Sequencing (NGS) techniques we were able to determine a global, unbiased view of both the host and pathogen. We propose a model for how viral DNA replication results in the differential utilization of cellular factors that function in transcription initiation. Our work outlines the various cis- and trans- acting factors utilized by the virus for this complex transcriptional program. We further elucidated the critical role that the major viral transactivator, ICP4, plays throughout the life cycle. We found that ICP4 coated the viral genome early during infection, and that rather than occluding the genome, this dense binding was associated with recruitment of the Pol II machinery to viral promoters. ICP4 discriminately bound the viral genome due to the absence of cellular nucleosomes and high density of cognate binding sites. We posit that ICP4’s ability to recruit components of the Pol II machinery to the viral genome creates a competitive transcriptional environment. These distinguishing characteristics ultimately result in a rapid and efficient reprogramming of the host’s transcriptional machinery.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
15 April 2020 |
| Date Type: |
Publication |
| Defense Date: |
20 March 2020 |
| Approval Date: |
15 April 2020 |
| Submission Date: |
25 March 2020 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
147 |
| 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: |
HSV-1, Viral Transcription Regulation, ICP4, Chromatin |
| Date Deposited: |
15 Apr 2020 12:05 |
| Last Modified: |
15 Apr 2020 12:05 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/38386 |
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