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Lysine Methylation as a Novel Regulatory Mechanism of HPV E2 Function

Award Number: R21AI199466
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: 05/06/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2028

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Lysine Methylation as a Novel Regulatory Mechanism of HPV E2 Function - PROJECT ABSTRACT Human papillomaviruses (HPV) are double-stranded DNA viruses that infect cutaneous and mucosal epithelia. Infections with high-risk HPVs may lead to cervical, anogenital, and oropharyngeal cancers accounting for 5% of all cancers worldwide. Currently there are no effective non-invasive treatments against high-risk HPV infections. Because of that, it is critical to study the fundamental biology of high-risk HPV and specifically its utilization of host cell factors to permit completion of its viral life cycle. The viral replicative program consists of three different stages: (1) initial replication after infection, (2) stable maintenance of viral genomes and (3) amplification of viral episomes. The PV activator E2 and E1 DNA helicase proteins are the first proteins to be expressed after infection and are essential for HPV replication. The viral E2 protein is necessary for replication of the viral genome, activation of the viral early promoter for transcription, and tethering of viral genomes to host mitotic chromosomes in basal cells during cellular replication and division. Our long-term goal is to elucidate host factors necessary for E1-E2 dependent HPV replication and E2-mediated transcription throughout the viral lifecycle. Protein lysine methylation is emerging as an important post-translational modification that regulates the activity of transcription factors and histones. We recently identified four lysine residues methylated within the HPV-31 E2 by mass spectrometry confirming that E2 is a methylated protein. We hypothesize that that lysine methylation is an important regulatory process during the viral lifecycle. The overall objectives in this application are to (i) identify the lysine methyl transferases responsible for E2 methylation and (ii) determine their biological function. The proposed research is significant because it will define the mechanisms tightly controlled by E2 methylation throughout the HPV lifecycle. Ultimately, such knowledge has the potential to target mechanisms of persistent HPV infections.


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 = $208,880 )
2026	2026	MARIAN UNIVERSITY INC	3200 COLD SPRING RD	INDIANAPOLIS	IN	46222	MARION	USA	Allergy and Infectious Diseases Research	000	1	5/7/2026	NEW	$208,880
														Subtotal = $208,880

Grand Total All Awards = $208,880

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Lysine Methylation as a Novel Regulatory Mechanism of HPV E2 Function

Award Number: R21AI199466

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: 05/06/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2028

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