期刊
VIROLOGY
卷 449, 期 -, 页码 304-316出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2013.10.038
关键词
L2; Minor capsid protein; Papillomavirus; Furin; Infectious intermediate; Neutralization; Human papillomavirus (HPV); Heparin; Carrageenan; Gamma secretase
类别
资金
- NCI NIH HHS [P50 CA098252, R01 CA118790, R01 CA133749] Funding Source: Medline
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 gamma-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. (C) 2013 Elsevier Inc. All rights reserved.
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