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

Joshua W. Wang, Subhashini Jagu, Kihyuck Kwak, Chenguang Wang, Shiwen Peng, Reinhard Kirnbauer, Richard B.S. Roden

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)304-316
Number of pages13
JournalVirology
Volume449
DOIs
StatePublished - Jan 20 2014

Keywords

  • Carrageenan
  • Furin
  • Gamma secretase
  • Heparin
  • Human papillomavirus (HPV)
  • Infectious intermediate
  • L2
  • Minor capsid protein
  • Neutralization
  • Papillomavirus

ASJC Scopus subject areas

  • Virology

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