Polyanionic Sugars Drastically Affect Assembly of Human Papilloma Virus Virus-Like Particles.

Area of Science:

• Virology
• Biochemistry
• Materials Science

Background:

• Human papillomavirus 16 (HPV16) L1 capsid protein forms virus-like particles (VLPs).
• Polysaccharide interactions with viruses can modulate host cell association and entry.
• Anionic polysaccharides heparin and carrageenan bind to HPV16 L1 and inhibit cell entry.

Purpose of the Study:

• To investigate if anionic polysaccharides can act as scaffolds to promote VLP assembly.
• To determine the structural features of anionic polysaccharides critical for modulating VLP assembly.

Main Methods:

• Studied the effect of heparin and κ-carrageenan on HPV16 L1 VLP assembly kinetics and stability.
• Assessed the impact of various anions on L1 pentamer assembly.
• Analyzed the susceptibility of L1 pentamers to proteolysis in the presence of heparin.

Main Results:

• Heparin, a flexible and highly sulfated polysaccharide, increased the rate and stability of L1 VLP assembly.
• κ-carrageenan, a rigid and less sulfated polysaccharide, inhibited L1 VLP assembly and destabilized existing VLPs.
• Smaller anions required higher concentrations to influence assembly, and chemical nature was also significant.

Conclusions:

• Artificial binding partners, specifically anionic polysaccharides, can control VLP assembly by interacting with the capsid protein exterior.
• Polysaccharide structural characteristics beyond size and electrostatics are critical for modulating self-assembly kinetics and stability.
• This work provides insights into controlling VLP assembly for potential applications in vaccine development and nanotechnology.