Human Papillomavirus infection requires the CCT Chaperonin Complex

Area of Science:

• Virology
• Cellular Biology
• Molecular Biology

Background:

• Human papillomavirus (HPV) infection involves complex interactions between viral proteins and host cellular machinery.
• The HPV L1 and L2 structural proteins are critical for viral entry and intracellular trafficking.
• The precise roles of cellular chaperones in HPV infection remain incompletely understood.

Purpose of the Study:

• To identify novel cellular interaction partners of the HPV-16 L2 protein.
• To investigate the role of the CCT chaperonin complex in HPV infectious entry.

Main Methods:

• Proteomic studies to identify HPV-16 L2 interacting proteins.
• Analysis of CCT subunit binding to HPV-16 L2.
• siRNA-mediated knockdown of CCT subunits to assess effects on HPV pseudoviral particle (PsVs) infection.
• Confocal immunofluorescence assays to determine co-localization of CCT3 and HPV PsVs.
• Assessment of capsid uncoating and intracellular processing of PsVs.

Main Results:

• CCT proteins were identified as novel interaction partners of HPV-16 L2.
• The interaction between HPV-16 L2 and CCT subunit 3 (CCT3) was confirmed and mapped to the N-terminal region of L2.
• Depletion of CCT subunits, particularly CCT2 and CCT3, significantly reduced HPV PsV infectivity.
• CCT3 co-localized with HPV PsVs upon infection, dependent on L2.
• Ablation of CCT3 impaired HPV PsV capsid uncoating and altered intracellular processing.

Conclusions:

• The CCT chaperonin complex is essential for efficient HPV infectious entry.
• CCT3 directly interacts with HPV-16 L2, playing a key role in viral processing and trafficking.
• The findings reveal a novel cellular mechanism supporting HPV infection, involving the CCT chaperonin complex.