ADAM17-dependent signaling is required for oncogenic human papillomavirus entry platform assembly

Area of Science:

• Cellular biology
• Virology
• Molecular interactions

Background:

• Oncogenic human papillomaviruses (HPV) infect keratinocytes, utilizing cell surface receptors for entry.
• Key molecular players in HPV entry include tetraspanin CD151 and epidermal growth factor receptor (EGFR).
• The spatial and temporal coordination of these components during HPV infection remains unclear.

Purpose of the Study:

• To investigate the plasma membrane dynamics of CD151 and EGFR during the early phase of HPV16 infection.
• To elucidate the role of ADAM17 and the ERK1/2 pathway in HPV entry platform formation.

Main Methods:

• Studied plasma membrane dynamics of CD151, EGFR, and HPV16 capsid.
• Investigated the role of the proteinase ADAM17 and the ERK1/2 signaling pathway.
• Analyzed the composition of infectious endocytic entry platforms.

Main Results:

• ADAM17 activates the ERK1/2 pathway by shedding growth factors, initiating endocytic entry platform formation.
• Infectious entry platforms are larger CD151 domains containing EGFR and HPV particles.
• Distinguished initial virus binding from ADAM17-dependent assembly of the HPV/CD151/EGFR entry platform.

Conclusions:

• ADAM17-mediated signaling is crucial for assembling the HPV entry platform.
• The study clarifies the distinct roles of virus binding and platform assembly in HPV infection.
• Findings provide insights into the molecular mechanisms of HPV cellular internalization.