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Regulation of the Human Papillomavirus Life Cycle by the Long Noncoding RNA DINO

Award Number: R01AI170633
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: 06/01/2023
PERIOD OF PERFORMANCE END DATE: 05/31/2028

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Regulation of the Human Papillomavirus Life Cycle by the Long Noncoding RNA DINO - Despite the currently available effective prophylactic vaccines, human papilloma virus infections remain the most common cause of venereal disease. Human papilloma virus-associated diseases are particularly prevalent in medically underserved segments of the population. Despite decades of research, there are no strategies that can limit the spread of human papilloma viruses. The productive viral life cycle of these viruses has been studied extensively, but research has almost exclusively focused on the contributions of viral and cellular proteins and protein-coding mRNAs. However, most of the cellular transcriptome does not encode proteins. Some non-coding RNAs likely represent functionally irrelevant transcriptional noise but several classes of non-coding RNAs serve important regulatory functions. Long non-coding RNAs have only recently emerged as critical modulators of many cellular regulatory circuits. Human papilloma viruses replicate their genomes to high copy numbers and generate progeny virus in terminally differentiated epithelial cells. We showed that expression of the long non-coding RNA DINO increases during epithelial differentiation and that ectopic expression of the long noncoding RNA DINO in a patient-derived, human papillomavirus episome- containing cell line causes an increase in viral genomes. This proposal addresses the hypothesis that DINO plays a previously unanticipated role in regulating the differentiation-dependent life cycle of human papillomaviruses. We will deploy a combination of biochemical, cell and molecular biology approaches to define the biological activities of DINO in human papillomavirus genome replication in dividing and differentiated viral episome-containing, patient-derived cell lines. The results from our studies will yield novel molecular insights into the differentiation-dependent life cycle of human papillomaviruses.


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: 2025 ( Subtotal = $418,426 )
2025	2025	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	3	6/12/2025	NON-COMPETING CONTINUATION	$418,426
														Subtotal = $418,426

Issue Date FY: 2024 ( Subtotal = $418,426 )
2024	2024	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	2	5/22/2024	NON-COMPETING CONTINUATION	$418,426
														Subtotal = $418,426

Issue Date FY: 2023 ( Subtotal = $418,426 )
2023	2023	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	1	5/31/2023	NEW	$418,426
														Subtotal = $418,426

Grand Total All Awards = $1,255,278

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Regulation of the Human Papillomavirus Life Cycle by the Long Noncoding RNA DINO

Award Number: R01AI170633

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: 06/01/2023

PERIOD OF PERFORMANCE END DATE: 05/31/2028

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