ATP synthase modulation leads to an increase of spare respiratory capacity in HPV associated cancers

Sci Rep. 2020 Oct 15;10(1):17339. doi: 10.1038/s41598-020-74311-6.


Mucosal and skin cancers are associated with infections by human papillomaviruses (HPV). The manner how viral oncoproteins hijack the host cell metabolism to meet their own energy demands and how this may contribute to tumorigenesis is poorly understood. We now show that the HPV oncoprotein E7 of HPV8, HPV11 and HPV16 directly interact with the beta subunit of the mitochondrial ATP-synthase (ATP5B), which may therefore represent a conserved feature across different HPV genera. By measuring both glycolytic and mitochondrial activity we observed that the association of E7 with ATP5B was accompanied by reduction of glycolytic activity. Interestingly, there was a drastic increase in spare mitochondrial respiratory capacity in HPV8-E7 and an even more profound increase in HPV16-E7 expressing cells. In addition, we could show that ATP5B levels were unchanged in betaHPV positive skin cancers. However, comparing HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas (OPSCC) we noticed that, while ATP5B expression levels did not correlate with patient overall survival in HPV-negative OPSCC, there was a strong correlation within the HPV16-positive OPSCC patient group. These novel findings provide evidence that HPV targets the host cell energy metabolism important for viral life cycle and HPV-mediated tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alphapapillomavirus / isolation & purification*
  • Female
  • Humans
  • Mitochondrial Proton-Translocating ATPases / metabolism*
  • Oncogene Proteins, Viral / metabolism
  • Oropharyngeal Neoplasms / virology*
  • Oxidative Phosphorylation
  • Papillomavirus Infections / metabolism*
  • Protein Binding
  • Squamous Cell Carcinoma of Head and Neck / virology*
  • Survival Analysis
  • Tumor Virus Infections / metabolism*


  • Oncogene Proteins, Viral
  • Mitochondrial Proton-Translocating ATPases