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Preparation and properties of a papillomavirus infectious intermediate and its utility for neutralization studies.

Abstract
We show that minor capsid protein L2 is full length in clinical virion isolates and prepare furin-cleaved pseudovirus (fcPsV) as a model of the infectious intermediate for multiple human papillomavirus (HPV) types. These fcPsV do not require furin for in vitro infection, and are fully infectious in vivo. Both the γ-secretase inhibitor XXI and carrageenan block fcPsV infection in vitro and in vivo implying that they act after furin-cleavage of L2. Despite their enhanced exposure of L2 epitopes, vaccination with fcPsV particles fails to induce L2 antibody, although L1-specific responses are similar to PsV with intact L2. FcPsV can be applied in a simple, high-throughput neutralization assay that detects L2-specific neutralizing antibodies with >10-fold enhanced sensitivity compared with the PsV-based assay. The PsV and fcPsV-based assays exhibit similar sensitivity for type-specific antibodies elicited by L1 virus-like particles (VLP), but the latter improves detection of L1-specific cross-type neutralizing antibodies.
AuthorsJoshua W Wang, Subhashini Jagu, Kihyuck Kwak, Chenguang Wang, Shiwen Peng, Reinhard Kirnbauer, Richard B S Roden
JournalVirology (Virology) Vol. 449 Pg. 304-16 (Jan 20 2014) ISSN: 1096-0341 [Electronic] United States
PMID24418565 (Publication Type: Journal Article)
Copyright© 2013 Published by Elsevier Inc.
Chemical References
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Capsid Proteins
  • Papillomavirus Vaccines
  • Furin
Topics
  • Alphapapillomavirus (genetics, immunology, physiology)
  • Animals
  • Antibodies, Neutralizing (immunology)
  • Antibodies, Viral (immunology)
  • Capsid Proteins (administration & dosage, genetics, immunology)
  • Cross Reactions
  • Furin (metabolism)
  • Humans
  • Mice, Inbred BALB C
  • Neutralization Tests
  • Papillomavirus Infections (immunology, prevention & control, virology)
  • Papillomavirus Vaccines (administration & dosage, genetics, immunology)

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