Bissett Sara L, Godi Anna, Fleury Maxime J J, Touze Antoine, Cocuzza Clementina, Beddows Simon
Virus Reference Department, Public Health England, London, United Kingdom.
GEIHP, UPRES EA 3142, Université d'Angers, Angers, France.
J Virol. 2015 Aug;89(15):7748-57. doi: 10.1128/JVI.00842-15. Epub 2015 May 20.
We investigated naturally occurring variation within the major (L1) and minor (L2) capsid proteins of oncogenic human papillomavirus (HPV) genotype 31 (HPV31) to determine the impact on capsid antigenicity. L1L2 pseudoviruses (PsVs) representing the three HPV31 variant lineages, variant lineages A, B, and C, exhibited comparable particle-to-infectivity ratios and morphologies. Lineage-specific L1L2 PsVs demonstrated subtle differences in susceptibility to neutralization by antibodies elicited following vaccination or preclinical L1 virus-like particle (VLP) immunization or by monoclonal antibodies; however, these differences were generally of a low magnitude. These data indicate that the diagnostic lineage-specific single nucleotide polymorphisms within the HPV31 capsid genes have a limited effect on L1 antibody-mediated neutralization and that the three HPV31 variant lineages belong to a single L1 serotype. These data contribute to our understanding of HPV L1 variant antigenicity.
The virus coat (capsid) of the human papillomavirus contains major (L1) and minor (L2) capsid proteins. These proteins facilitate host cell attachment and viral infectivity and are the targets for antibodies which interfere with these events. In this study, we investigated the impact of naturally occurring variation within these proteins upon susceptibility to viral neutralization by antibodies induced by L1 VLP immunization. We demonstrate that HPV31 L1 and L2 variants exhibit similar susceptibility to antibody-mediated neutralization and that for the purposes of L1 VLP-based vaccines, these variant lineages represent a single serotype.
我们研究了致癌性人乳头瘤病毒31型(HPV31)主要衣壳蛋白(L1)和次要衣壳蛋白(L2)中的自然变异,以确定其对衣壳抗原性的影响。代表HPV31三个变异谱系,即A、B和C变异谱系的L1L2假病毒(PsV),其颗粒感染率和形态具有可比性。谱系特异性L1L2 PsV在疫苗接种或临床前L1病毒样颗粒(VLP)免疫后诱导产生的抗体或单克隆抗体对其进行中和的敏感性方面表现出细微差异;然而,这些差异通常较小。这些数据表明,HPV31衣壳基因内的诊断性谱系特异性单核苷酸多态性对L1抗体介导的中和作用影响有限,且HPV31的三个变异谱系属于单一L1血清型。这些数据有助于我们理解HPV L1变异体的抗原性。
人乳头瘤病毒的病毒外壳(衣壳)包含主要衣壳蛋白(L1)和次要衣壳蛋白(L2)。这些蛋白促进宿主细胞附着和病毒感染性,并且是干扰这些事件的抗体的靶标。在本研究中,我们调查了这些蛋白中的自然变异对L1 VLP免疫诱导的抗体对病毒中和敏感性的影响。我们证明,HPV31 L1和L2变异体对抗体介导的中和作用表现出相似的敏感性,并且就基于L1 VLP的疫苗而言,这些变异谱系代表单一血清型。