Differentiated Oral Epithelial Cells Support the HPV Life Cycle

Area of Science:

• Oral biology
• Virology
• Cellular biology

Background:

• Increasing incidence of Human Papillomavirus (HPV) associated oral diseases necessitates better research models.
• Current models for studying oral HPV infection are limited and labor-intensive.

Approach:

• Investigated the ability of differentiated oral epithelial cells (OKF6tert1) to support the HPV life cycle.
• Introduced HPV16 episomes and utilized sodium butyrate to induce varying degrees of cellular differentiation.
• Analyzed viral and cellular gene expression, differentiation markers, DNA damage responses, and viral particle production.

Key Points:

• HPV16 infection altered the differentiation pathway of oral epithelial cells, increasing mitotic and suprabasal markers while decreasing terminal differentiation markers.
• Both early and late viral gene products, including spliced mRNAs and proteins (E7, L1), were detected.
• Evidence of permissive HPV replication was observed, including DNA damage responses, LCR transactivation, and the formation of DNase-resistant particles.

Conclusions:

• Differentiated, immortalized oral epithelial cells can support the complete HPV life cycle.
• HPV may manipulate the differentiation state of oral epithelial cells to promote its own replication.