The fanconi anemia pathway limits human papillomavirus replication

Area of Science:

• Oncology
• Virology
• Genetics

Background:

• High-risk human papillomaviruses (HPVs) cause squamous cell carcinomas (SCCs), with HPV-positive head and neck SCCs increasing.
• Fanconi anemia (FA) is a genome instability disorder predisposing individuals to SCCs.
• The role of genetic factors in regulating HPV oncogene expression and genome load is poorly understood.

Purpose of the Study:

• To investigate the role of the Fanconi anemia (FA) pathway in regulating human papillomavirus (HPV) oncogene expression and genome amplification.
• To determine if FA pathway components suppress HPV infection and disease progression.

Main Methods:

• Studied the effect of FANCA and FANCD2 loss on HPV E7 protein accumulation in human keratinocytes.
• Assessed epithelial proliferation and basal cell layer expansion in HPV-positive epidermis with FANCD2 loss.
• Examined HPV genome amplification in differentiating cells lacking FANCD2.

Main Results:

• Loss of FA pathway components FANCA and FANCD2 stimulates HPV E7 protein accumulation.
• FANCD2 loss increases epithelial proliferation and basal cell layer expansion in HPV-positive epidermis.
• FANCD2 deficiency enhances HPV genome amplification in differentiating cells, indicating the FA pathway restricts the HPV life cycle.

Conclusions:

• The intact FA pathway functions to restrict the HPV life cycle.
• FA genes may suppress HPV infection and related SCC development.
• Findings suggest mechanisms for observed associations between HPV and FA cohorts, and HPV persistence with FA gene variations.