# Regulation of human papillomavirus pathogenesis by long non-coding RNAs

> **NIH NIH R21** · TUFTS UNIVERSITY BOSTON · 2020 · $202,350

## Abstract

ABSTRACT
Mucosotropic human papillomaviruses (HPVs) are sexually transmitted agents and more than 80% of the
population will experience an HPV infection during their life time. Despite the availability of excellent
prophylactic vaccines, the disease burden caused by these viruses has not markedly decreased. No HPV
specific antiviral compounds are on the market and the clinical management of HPV-associated lesions
remains based on painful, invasive, ablative procedures. The HPV E6 and E7 genes are the main drivers of
disease. E7 plays a key role in enabling the viral life cycle in terminally differentiated, post-mitotic epithelial
cells by subverting major cellular pathways that signal growth arrest during differentiation. As a consequence,
the failure to enact a growth arrest during differentiation causes activation of TP53, a transcription factor that
induces expression of coding and non-coding genes that enact a cytotoxic response. In HPV infected cells, this
cell-abortive TP53 response to E7 expression is muted by the co-expressed HPV E6 protein which targets
TP53 for degradation. Inactivation of E6 reactivates the dormant TP53 response and triggers death of HPV
infected cells. Because there are no methods available to directly inhibit E6, we propose to investigate
whether TP53 mediated cell death is reactivated by modulating expression of molecules that cause TP53
activation and/or mediate the cytotoxic TP53 response. We have determined that two poorly studied long non-
coding (lnc)RNAs, DINO and TRINGS, play important roles in mediating TP53 activation by E7 and modulate
the cell death response to TP53 activation. Our proposal is based on the hypothesis that the dormant TP53
dependent cytotoxic response generated by E7 expression may be reactivated in HPV-infected cells by
modulation of DINO and/or TRINGS. The work that we propose here will focus on determining the mechanism
by which DINO (aim 1) and TRINGS (aim 2) modulate the TP53 mediated cell death response to metabolic
stress and other stimuli.

## Key facts

- **NIH application ID:** 9939445
- **Project number:** 5R21AI147176-02
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **Principal Investigator:** Karl Munger
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $202,350
- **Award type:** 5
- **Project period:** 2019-06-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939445

## Citation

> US National Institutes of Health, RePORTER application 9939445, Regulation of human papillomavirus pathogenesis by long non-coding RNAs (5R21AI147176-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9939445. Licensed CC0.

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