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Modulation of herpes simplex virus type 1 genome structure during lytic replication

Award Number: R21AI166879
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/24/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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Modulation of herpes simplex virus type 1 genome structure during lytic replication - Herpes simplex virus type 1 (HSV-1) is a prevalent pathogen that infects the majority of the human population. Much of the virus life cycle occurs in the nucleus of infected cells, where events that occur on the viral genome determine the outcome of infection. However, how the structure of the viral DNA contributes to the regulation of key viral processes is not well understood. Virion HSV-1 DNA enters into host cells containing single strand breaks and single stranded gaps. During viral DNA replication, branched genome structures form, likely as recombination-mediated replication intermediates. We previously demonstrated that distinct groups of cellular DNA repair proteins associate with viral genomes early during infection and after the onset of viral DNA replication. How DNA damage is navigated by viral DNA replication, transcription, and packaging machinery is not understood. Furthermore, how the genome-wide structure of the HSV-1 genome is modified during the temporal progression of infection has not been defined. A major roadblock to previously investigate these questions was the inability to probe genome-wide DNA structure. In this exploratory proposal, we describe our plan to develop approaches to define the structure of the HSV-1 genome throughout productive infection. The aims outlined in this proposal will establish new approaches to map single and double strand breaks on HSV-1 DNA and investigate viral replication and recombination intermediates in vivo. Results will provide greater insight into mechanisms of regulation of HSV-1 transcription, DNA replication, recombination, and repair. Furthermore, tools generated could be adapted to probe HSV-1 genomes before and after reactivation, viral infection in cells deficient for select cellular DNA repair and DNA damage response factors, and genomes of other DNA viruses.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = -$442 )
2026	2022	DUQUESNE UNIVERSITY OF THE HOLY SPIRIT	600 FORBES AVENUE	PITTSBURGH	PA	15282	ALLEGHENY	USA	Allergy and Infectious Diseases Research	000	2	2/5/2026	NON-COMPETING CONTINUATION	-$442
														Subtotal = -$442

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	DUQUESNE UNIVERSITY OF THE HOLY SPIRIT	600 FORBES AVENUE	PITTSBURGH	PA	15282	ALLEGHENY	USA	Allergy and Infectious Diseases Research	000	2	7/15/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $207,000 )
2022	2022	DUQUESNE UNIVERSITY OF THE HOLY SPIRIT	600 FORBES AVENUE	PITTSBURGH	PA	15282	ALLEGHENY	USA	Allergy and Infectious Diseases Research	000	2	8/17/2022	NON-COMPETING CONTINUATION	$207,000
														Subtotal = $207,000

Issue Date FY: 2021 ( Subtotal = $172,500 )
2021	2021	DUQUESNE UNIVERSITY OF THE HOLY SPIRIT	600 FORBES AVE	PITTSBURGH	PA	15282	ALLEGHENY	USA	Allergy and Infectious Diseases Research	000	1	9/24/2021	NEW	$172,500
														Subtotal = $172,500

Grand Total All Awards = $379,058

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Modulation of herpes simplex virus type 1 genome structure during lytic replication

Award Number: R21AI166879

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/24/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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