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Maturation of papillomavirus capsids
Christopher B Buck1, Cynthia D Thompson, Yuk-Ying S Pang
1Laboratory of Cellular Oncology, Building 37, Room 4106, 9000 Rockville Pike, Bethesda, MD 20892-4263, USA.
Journal of Virology
|February 15, 2005
Summary
Papillomavirus capsid maturation involves overnight disulfide bond formation, stabilizing the structure. This process is crucial for producing robust gene transfer vectors, though it doesn't affect antibody neutralization.
Area of Science:
- Virology
- Structural Biology
- Biochemistry
Background:
- Papillomavirus capsids are icosahedral shells made of L1 protein.
- Disulfide bonds between L1 proteins stabilize the capsid.
- Kinetics of disulfide bond formation during morphogenesis were previously unexamined.
Purpose of the Study:
- To investigate the kinetics of inter-L1 disulfide bond formation during papillomavirus capsid maturation.
- To understand the role of disulfide bonds in capsid stabilization and vector production.
Main Methods:
- Production of high-titer papillomavirus-based gene transfer vectors (pseudoviruses) in mammalian cells.
- Analysis of capsid maturation process, focusing on disulfide bond formation.
- Comparison of maturation kinetics and structures for different papillomavirus types (HPV16, HPV18, BPV1).
Main Results:
- Papillomavirus capsid maturation is driven by inter-L1 disulfide bond formation, requiring overnight incubation.
- Mature capsids show increased regularity and resistance to proteolysis.
- Maturation pathways differ between HPV and BPV, with L1 dimers/trimers forming in HPV and extensive cross-linking in BPV.
- Encapsidated DNA and L2 protein had minimal impact on maturation kinetics.
Conclusions:
- Capsid maturation is essential for efficient purification of papillomavirus gene transfer vectors.
- Immature capsids are infectious but fragile, while mature capsids are stabilized.
- Antibody neutralization is similar for both mature and immature capsids.