Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou 571199, China.
Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Hainan Medical University, Haikou 571199, China.
Viruses. 2021 Oct 13;13(10):2058. doi: 10.3390/v13102058.
Human noroviruses are a common pathogen causing acute gastroenteritis worldwide. Among all norovirus genotypes, GII.3 is particularly prevalent in the pediatric population. Here we report the identification of two distinct blockade antibody epitopes on the GII.3 capsid. We generated a panel of monoclonal antibodies (mAbs) from mice immunized with virus-like particle (VLP) of a GII.3 cluster 3 strain. Two of these mAbs, namely 8C7 and 8D1, specifically bound the parental GII.3 VLP but not VLPs of GII.4, GII.17, or GI.1. In addition, 8C7 and 8D1 efficiently blocked GII.3 VLP binding with its ligand, histo-blood group antigens (HBGA). These data demonstrate that 8C7 and 8D1 are GII.3-specific blockade antibodies. By using a series of chimeric VLPs, we mapped the epitopes of 8C7 and 8D1 to residues 385-400 and 401-420 of the VP1 capsid protein, respectively. These two blockade antibody epitopes are highly conserved among GII.3 cluster 3 strains. Structural modeling shows that the 8C7 epitope partially overlaps with the HBGA binding site (HBS) while the 8D1 epitope is spatially adjacent to HBS. These findings may enhance our understanding of the immunology and evolution of GII.3 noroviruses.
人类诺如病毒是一种常见的病原体，可在全球范围内引起急性胃肠炎。在所有诺如病毒基因型中，GII.3 在儿科人群中尤为流行。在这里，我们报告了在 GII.3 衣壳上鉴定出两个不同的阻断抗体表位。我们从用病毒样颗粒（VLP）免疫的小鼠中生成了一组单克隆抗体（mAb），该 VLP 来自 GII.3 簇 3 株。其中两种 mAb，即 8C7 和 8D1，特异性结合亲本 GII.3 VLP，但不结合 GII.4、GII.17 或 GI.1 的 VLP。此外，8C7 和 8D1 可有效地阻断 GII.3 VLP 与其配体——组织血型抗原（HBGA）的结合。这些数据表明 8C7 和 8D1 是 GII.3 特异性阻断抗体。通过使用一系列嵌合 VLP，我们将 8C7 和 8D1 的表位分别映射到 VP1 衣壳蛋白的 385-400 位和 401-420 位残基上。这两个阻断抗体表位在 GII.3 簇 3 株中高度保守。结构建模表明，8C7 表位部分与 HBGA 结合位点（HBS）重叠，而 8D1 表位与 HBS 空间相邻。这些发现可能会增进我们对 GII.3 诺如病毒免疫学和进化的理解。
