1Virus Reference Department, Public Health England, London, UK.
†Present address: Retrovirus-Host Interactions Laboratory, The Francis Crick Institute, 1 Midland Road, London, UK.
J Gen Virol. 2019 Feb;100(2):237-245. doi: 10.1099/jgv.0.001213. Epub 2019 Jan 18.
We investigated the impact of naturally occurring variation within the major (L1) and minor (L2) capsid proteins on the antigenicity of human papillomavirus (HPV) type 52 (HPV52). L1L2 pseudoviruses (PsVs) representing HPV52 lineage and sublineage variants A1, A2, B1, B2, C and D were created and tested against serum from naturally infected individuals, preclinical antisera raised against HPV52 A1 and D virus-like particles (VLPs) and neutralising monoclonal antibodies (MAbs) raised against HPV52 A1 VLP. HPV52 lineage D PsV displayed a median 3.1 (inter-quartile range 2.0-5.6) fold lower sensitivity to antibodies elicited following natural infection with, where data were available, HPV52 lineage A. HPV52 lineage variation had a greater impact on neutralisation sensitivity to pre-clinical antisera and MAbs. Chimeric HPV52 A1 and D PsV were created which identified variant residues in the FG (Q281K) and HI (K354T, S357D) loops as being primarily responsible for the reported differential sensitivities. Homology models of the HPV52 L1 pentamer were generated which permitted mapping these residues to a small cluster on the outer rim of the surface exposed pentameric L1 protein. These data contribute to our understanding of HPV L1 variant antigenicity and may have implications for seroprevalence or vaccine immunity studies based upon HPV52 antigens.
我们研究了主要（L1）和次要（L2）衣壳蛋白中自然发生的变异对人乳头瘤病毒（HPV）52 型（HPV52）抗原性的影响。代表 HPV52 谱系和亚谱系变体 A1、A2、B1、B2、C 和 D 的 L1L2 假病毒（PsV）被创建并针对来自自然感染个体的血清、针对 HPV52 A1 和 D 病毒样颗粒（VLPs）的临床前抗血清以及针对 HPV52 A1 VLP 的中和单克隆抗体（MAb）进行了测试。HPV52 谱系 D PsV 对自然感染 HPV52 谱系 A 后产生的抗体的敏感性降低了中位数 3.1 倍（四分位距 2.0-5.6）。HPV52 谱系的变异对临床前抗血清和 MAb 的中和敏感性有更大的影响。创建了 HPV52 A1 和 D 的嵌合 PsV，鉴定了 FG（Q281K）和 HI（K354T、S357D）环中的变体残基是导致报道的敏感性差异的主要原因。生成了 HPV52 L1 五聚体的同源模型，允许将这些残基映射到表面暴露的五聚体 L1 蛋白外边缘的一小簇上。这些数据有助于我们了解 HPV L1 变体的抗原性，并且可能对基于 HPV52 抗原的血清流行率或疫苗免疫研究有影响。
