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Virology. 2014 Jan 20;449:304-16. doi: 10.1016/j.virol.2013.10.038. Epub 2013 Dec 20.

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

Author information

1
Department of Pathology, The Johns Hopkins University, Baltimore, MD 21231, USA.
2
Department of Biostatistics, The Johns Hopkins University, Baltimore, MD 21231, USA.
3
Department of Oncology, The Johns Hopkins University, Baltimore, MD 21231, USA.
4
Laboratory of Viral Oncology, Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University Vienna (MUW), Vienna, Austria.
5
Department of Pathology, The Johns Hopkins University, Baltimore, MD 21231, USA; Department of Oncology, The Johns Hopkins University, Baltimore, MD 21231, USA; Department of Gynecology and Obstetrics, The Johns Hopkins University, Baltimore, MD 21231, USA. Electronic address: roden@jhmi.edu.

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.

KEYWORDS:

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

PMID:
24418565
PMCID:
PMC3932537
DOI:
10.1016/j.virol.2013.10.038
[Indexed for MEDLINE]
Free PMC Article

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