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Related Experiment Video

Updated: Jan 13, 2026

A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions
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Differentiation-dependent proximity proteomics identifies novel host factors linked to HPV16 E2 function.

Claire D James1,2, Aya Youssef1, Apurva T Prabhakar1,2

  • 1Virginia Commonwealth University (VCU), Philips Institute for Oral Health Research, School of Dentistry, Richmond, Virginia, USA.

Mbio
|January 12, 2026
PubMed
Summary

Human papillomavirus 16 (HPV16) E2 protein interactions were mapped in differentiating cells. A new cooperative axis involving E2, TOPBP1, and nucleolin (NCL) is crucial for HPV16 genome stability.

Keywords:
DNA damage responseE2 proteinTOPBP1human papillomavirus type 16 (HPV16)nucleolinprotein-protein interactionsproximity proteomicsviral life cycle

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Area of Science:

  • Virology
  • Molecular Biology
  • Cancer Research

Background:

  • Human papillomaviruses (HPVs) cause significant cancers and rely on host DNA repair factors for replication.
  • The HPV16 E2 protein is vital for viral genome replication, maintenance, and DNA damage response.
  • Understanding E2 interactions with host proteins, especially during differentiation, is key to viral persistence.

Purpose of the Study:

  • To comprehensively map the HPV16 E2 protein interactome in differentiating keratinocytes.
  • To investigate the role of host factor TOPBP1 in E2 interactions and viral genome maintenance.
  • To identify novel host factors critical for HPV16 replication and stability.

Main Methods:

  • Utilized TurboID proximity labeling in stable keratinocyte lines expressing tagged HPV16 E2.
  • Performed mass spectrometry to identify E2-associated proteins.
  • Validated interactions using proximity ligation assays and functional studies.

Main Results:

  • Identified known and novel host factors interacting with HPV16 E2, including chromatin regulators and DNA repair proteins.
  • Demonstrated substantial overlap between HPV16 E2 and TOPBP1 interactomes.
  • Discovered nucleolin (NCL) as a differentiation-dependent E2 partner, stabilized by TOPBP1, essential for episomal genome maintenance.

Conclusions:

  • The study reveals a cooperative E2-TOPBP1-NCL axis critical for HPV16 genome stability during differentiation.
  • HPV16 hijacks host chromatin and DNA repair networks for viral genome maintenance and replication.
  • This axis represents a potential new target for antiviral interventions against HPV infections.