HPV Capsid-Derived Cationic Peptides for Cargo Delivery and Antiviral Activity

Area of Science:

• Virology
• Biochemistry
• Drug Delivery

Background:

• High-risk Human Papillomaviruses (HR-HPVs) cause a significant portion of global cancers.
• Current treatments for HR-HPV infections are limited, with no options for already infected individuals.
• Cell-penetrating peptides (CPPs) show promise for antiviral therapies but face delivery challenges.

Purpose of the Study:

• To identify and characterize novel cell-penetrating peptides (CPPs) derived from Human Papillomavirus (HPV) capsid proteins.
• To evaluate the potential of these CPPs for delivering therapeutic agents and inhibiting HR-HPV infections.

Main Methods:

• Identification of a cationic peptide from the HPV16 major capsid protein L1.
• Investigation of peptide uptake mechanisms, including heparan sulfate-mediated and lipid-raft dependent endocytosis.
• Assessment of the peptide's ability to deliver GFP into keratinocytes and its antiviral activity against various HR-HPV types.

Main Results:

• An HPV16 L1-derived peptide was identified as a potent CPP, with uptake dependent on cationic residues and specific sequence.
• The peptide demonstrated efficient delivery of cargo (GFP) into HaCaT keratinocytes, with evidence of endosomal escape.
• The peptide exhibited broad-spectrum antiviral activity against multiple HR-HPV types, including inhibition of viral internalization by an HPV18 L1-derived peptide.

Conclusions:

• HPV-derived peptides function as highly efficient CPPs, overcoming common delivery challenges.
• These peptides show significant potential for developing novel therapeutic strategies against high-risk HPV infections.
• The findings pave the way for using HPV-derived peptides to deliver antiviral agents and treat HPV-associated cancers.