# Mechanisms of Infection by Oncogenic HPVs

> **NIH NIH R01** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2020 · $345,887

## Abstract

Project Summary/Abstract
The epidermal growth factor receptor (EGFR) has key regulatory roles in epithelial wound healing, cell growth
and cell survival in many mammalian cell types. EGFR is hijacked by many human viruses, including human
papillomaviruses (HPVs), to promote their infectious entry into host cells. Yet, specific mechanisms by which
EGFR activation leads to virion internalization are poorly understood. HPV types 16 and 31 interact with
EGFR and the EGFR-interacting partner, the annexin A2 tetramer (A2t), at the HK plasma membrane. Our
scientific premise is based on findings from our lab and from other groups: functional inhibition of EGFR or A2t
proteins significantly reduces HPV entry and infection in HKs. Our CENTRAL HYPOTHESIS is that EGFR
signaling promotes the translocation of A2t to the external cell membrane to initiate the infectious entry of HPV
into host cells. We will define the role that EGFR and its signaling plays in promoting HPV uptake in HKs, and
determine whether EGFR is directly involved in onco-HPV internalization. We will also examine how A2t
cooperates with EGFR signaling to facilitate infectious entry of onco-HPV. Epithelial wounding plays an
important, but poorly understood, role in papillomavirus infections in vivo. Notably, EGFR and A2t are
activated in epithelial wound settings. We will use infectious entry assays (detection of viral transcription or
pseudo-genome expression) coupled with biochemical and genetic cell manipulations to define the
mechanisms of HPV infection of normal host HKs. Quantitative multi-parameter confocal, super-resolution and
video microscopy will permit us to visualize the fate of HPVs and localize the viruses with cell proteins under
genetic and biochemical conditions that prevent infectious entry. We will combine the techniques described
above with cell culture and mouse models of infection where epithelial wounding can be induced to examine
how wounding contributes to HPV infections. Three inter-related SPECIFIC AIMS will address our central
hypothesis. In Aim 1 we will determine function of EGFR in onco-HPV entry into HKs. In Aim 2 we will
define how the interplay between EGFR and A2t promotes the uptake of onco-HPVs into HKs. In Aim 3 we will
assess the roles of EGFR and A2t in HPV entry in keratinocytes using in vitro and in vivo wound models.
Hypotheses regarding specific aspects of HPV-HK interactions, EGFR and AnxA2 activities and HPV entry are
posed. Whether our theories are supported or refuted, we will increase our understanding of the molecular
mechanisms of HPV-host cell interactions, the biology of HK uptake, and EGFR regulation in HKs, each of
which are poorly understood. This fundamental science program may also inform strategies for preventing
persistent onco-HPV infections, a major risk for morbidity and malignant progression. As EGFR and AnxA2
are important for other virus infections, our results may be applicable to these pathogens as well. Lastly, we
will gai...

## Key facts

- **NIH application ID:** 9936362
- **Project number:** 5R01CA207368-04
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Michelle A Ozbun
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $345,887
- **Award type:** 5
- **Project period:** 2017-06-09 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9936362

## Citation

> US National Institutes of Health, RePORTER application 9936362, Mechanisms of Infection by Oncogenic HPVs (5R01CA207368-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9936362. Licensed CC0.

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