Human Papilloma Virus (HPV) is a common virus with a high global prevalence of infection. There are over 200 types of HPV, and while outcomes from most infections are minor or self-limited, 17 types are implicated in the pathogenesis of nearly all cervical cancers, with HPV 16 and 18 being the predominant types. Proteins encoded by the HPV oncogenes E6 and E7 exert tumorigenic effects by cell cycle disruption, evasion of apoptosis, DNA damage and suppression of the host immune response, all via interactions with host proteins. For example, the oncoprotein E6 subverts the host E3 ubiquitin ligase E6-AP to target the tumor suppressor p53 for ubiquitin-mediated degradation, thereby disrupting apoptosis and genome stability. E6 also interacts with TNF-receptor 1 (TNFR1) and FADD to promote cell immortalization, as well as with PDZ-containing host proteins resulting in loss of cell polarity and adhesion. The oncoprotein E7 binds to and inactivates the RB tumor suppressor protein to deregulate cell cycle progression, and thereby synergizes with E6 to promote transformation.

The BioGRID HPV Curation Project aims to extensively curate the biomedical literature for HPV-host protein interactions to enable the understanding and interrogation of the complex viral-host network. This curated data will facilitate mechanistic understanding of HPV-mediated tumorigenesis, with the ultimate goal of identifying potential points of intervention in the treatment of cervical cancer. Additionally, because several of the same high risk HPV types have been implicated in the development of anal, vulvar, vaginal, penile, oropharyngeal and lung cancers, curation of the interactions between virally-encoded proteins and host cell proteins will also help inform pathogenic mechanisms and treatment strategies in these cancers.

The HPV project is being developed in collaboration with both experimental and computational groups using machine learning (ML)-based text analysis and will be expanded to include additional host genes and HPV types relevant to HPV-induced cancers. In this initial release, virus encoded proteins from the oncogenic HPV 16 and non-oncogenic HPV6b types comprise the query set for protein interaction curation.

The HPV curation project is on-going and will be updated each month. If you notice errors or missing interactions/publications in this dataset, or otherwise wish to contribute to this project, please contact us at biogridadmin@gmail.com. All HPV BioGRID database records are freely available for download from links within this project. The HPV curation project is funded by NIH grant R01 RR024031 and Gates Foundation grant INV-081342.