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Papillomavirus capsid proteins mutually impact structure

Horng-Shen Chen1, Michael J Conway, Neil D Christensen

  • 1Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.

Virology
|February 19, 2011
PubMed

Insights

Mutant human papillomavirus (HPV) capsid proteins reveal that changes in one protein affect the other. This suggests vaccines must consider variations in both HPV L1 and L2 capsid proteins for sustained effectiveness.

Area of Science:

  • Virology
  • Vaccine development
  • Structural biology

Background:

  • Human papillomavirus (HPV) is a common virus with two major capsid proteins, L1 and L2.
  • Current HPV vaccines primarily target the L1 protein.
  • Understanding the structural and antigenic interplay between L1 and L2 is crucial for vaccine efficacy.

Purpose of the Study:

  • To investigate the structural and antigenic effects of chimeric capsid proteins between HPV16 and HPV18.
  • To determine how variations in one capsid protein influence the other within the virion.
  • To assess the implications for HPV vaccine design and effectiveness.

Main Methods:

  • Construction and analysis of mutant viruses with wild-type and chimeric HPV16/HPV18 capsid proteins.
  • Assessment of capsid protein expression, genome amplification, and episomal maintenance.
  • Titration of chimeric viruses and comparison with wild-type.
  • Utilizing conformation-dependent neutralizing L1 monoclonal antibodies (MAbs) and an L2 capsid surface peptide antibody to probe structural changes.

Main Results:

  • Mutant and chimeric capsid protein expression, genome amplification, and episomal maintenance were comparable to wild-type.
  • Chimeric viruses exhibited variations in titers compared to wild-type viruses.
  • Intertypical mutant chimeric capsid viruses demonstrated that L2 affects L1 structure and L1 affects L2 structure within the virion.
  • Structural and antigenic changes in one capsid protein were observed to impact the other.

Conclusions:

  • Variation in one HPV capsid gene significantly impacts the structure and antigenicity of the other capsid protein.
  • The interplay between L1 and L2 capsid proteins is critical for virion integrity and antigenicity.
  • For sustained vaccine effectiveness, future strategies should consider variations in both HPV L1 and L2 capsid proteins, not solely the targeted protein.

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