制备和鉴定一种乳头瘤病毒感染中间体及其在中和研究中的应用。
Preparation and properties of a papillomavirus infectious intermediate and its utility for neutralization studies.
机构信息
Department of Pathology, The Johns Hopkins University, Baltimore, MD 21231, USA.
Department of Biostatistics, The Johns Hopkins University, Baltimore, MD 21231, USA.
出版信息
Virology. 2014 Jan 20;449:304-16. doi: 10.1016/j.virol.2013.10.038. Epub 2013 Dec 20.
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.
摘要
我们证明，临床病毒分离株中的次要衣壳蛋白 L2 是全长的，并制备了弗林蛋白酶切割的假病毒（fcPsV）作为多种人乳头瘤病毒（HPV）类型的感染中间体模型。这些 fcPsV 不需要弗林蛋白酶进行体外感染，并且在体内具有完全的感染性。γ-分泌酶抑制剂 XXI 和角叉菜胶均可阻断 fcPsV 在体外和体内的感染，这表明它们在 L2 的弗林蛋白酶切割之后起作用。尽管 fcPsV 颗粒增强了 L2 表位的暴露，但接种 fcPsV 颗粒未能诱导 L2 抗体，尽管 L1 特异性反应与具有完整 L2 的 PsV 相似。FcPsV 可应用于简单、高通量的中和测定中，与基于 PsV 的测定相比，该测定检测 L2 特异性中和抗体的灵敏度提高了 10 倍以上。基于 PsV 和 fcPsV 的测定法对 L1 病毒样颗粒（VLP）诱导的型特异性抗体具有相似的敏感性，但后者提高了对 L1 特异性交叉型中和抗体的检测。
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