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EPIGENETIC REGULATION OF THE ESTABLISHMENT OF AN SV40 INFECTION

Award Number: R03AI142011
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: 12/01/2018
PERIOD OF PERFORMANCE END DATE: 11/30/2022

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EPIGENETIC REGULATION OF THE ESTABLISHMENT OF AN SV40 INFECTION - DNA viruses such as Simian Virus 40 (SV40) exploit cellular processes to control their own life cycle during an infection. In the proposed studies, we are using SV40 as a model to study the selective activation of gene expression in a chromatin environment. We will determine the role of nucleosome location and associated histone modifications present in the infecting virus on the infection-mediated remodeling of chromatin structure required for activating early SV40 genes while maintaining repression of the late genes. These studies are based upon the hypothesis that epigenetic information encoded into the chromatin of virions controls the chromatin remodeling resulting in the initiation of early transcription and repression of late transcription. The specific aims of this proposal are (1) to characterize the epigenetic changes occurring during a typical wild-type SV40 infection leading to the initiation of early transcription and (2) to characterize the initiation of infection and early transcription in epigenetically dysregulated SV40. The location of nucleosomes containing specific histone modifications in SV40 minichromosomes obtained from wild-type and epigenetically dysregulated virus early in infection and in uncoating intermediates from wild-type virus will be determined using ChIP-Seq. Our proposed studies will inform us about events leading to initiation of infection such as: which nucleosomes change position, which histone modifications either decrease or increase during the initial stages of infection, when the changes occur, and the extent to which they depend upon active transcription. Analyzing SV40 chromatin that is transcriptionally poised, we will identify the chromatin elements responsible for repressing late transcription and whether specific nucleosome positioning or histone modifications are necessary at sites of active molecular biology such as the splice sites or the termination of transcription. The work is innovative because it will be the first analysis of the chromatin changes occurring during infection and will be the first analysis in which the location of nucleosomes and their histone modifications will be characterized in chromatin containing RNAPII during the activation of transcription. The studies are significant because they will lead to a better understanding of how nucleosome positioning is regulated by the presence of histone modifications. Additionally, our results will serve as a model for a number of related viruses that are significant human pathogens.


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: 2024 ( Subtotal = -$7,174 )
2024	2020	UNIVERSITY OF NORTH DAKOTA	264 CENTENNIAL DR STOP 8371	GRAND FORKS	ND	58202	GRAND FORKS	USA	Allergy and Infectious Diseases Research	000	2	10/23/2023	NON-COMPETING CONTINUATION	-$7,174
														Subtotal = -$7,174

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	UNIVERSITY OF NORTH DAKOTA	264 CENTENNIAL DR	GRAND FORKS	ND	58202	GRAND FORKS	USA	Allergy and Infectious Diseases Research	000	2	11/30/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $69,500 )
2020	2020	UNIVERSITY OF NORTH DAKOTA	264 CENTENNIAL DR	GRAND FORKS	ND	58202	GRAND FORKS	USA	Allergy and Infectious Diseases Research	000	2	11/19/2019	NON-COMPETING CONTINUATION	$69,500
														Subtotal = $69,500

Issue Date FY: 2019 ( Subtotal = $69,500 )
2019	2019	UNIVERSITY OF NORTH DAKOTA	264 CENTENNIAL DR	GRAND FORKS	ND	58202	GRAND FORKS	USA	Allergy and Infectious Diseases Research	000	1	11/27/2018	NEW	$69,500
														Subtotal = $69,500

Grand Total All Awards = $131,826

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EPIGENETIC REGULATION OF THE ESTABLISHMENT OF AN SV40 INFECTION

Award Number: R03AI142011

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: 12/01/2018

PERIOD OF PERFORMANCE END DATE: 11/30/2022

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