The Sixth People's Hospital of Zhengzhou, Zhengzhou 450000, China.
The Sixth People's Hospital of Zhengzhou, Zhengzhou 450000, China.
Virus Res. 2023 Sep;334:199168. doi: 10.1016/j.virusres.2023.199168. Epub 2023 Jun 30.
Noroviruses (NoVs) are the leading agent that causes acute viral gastroenteritis worldwide. Sporadic cases of GII.6 NoV have been reported primarily in addition to occasional outbreaks. Using the major capsid protein VP1 of GII.6 NoV derived from three distinct clusters, we demonstrated three blockade monoclonal antibodies (mAbs, 1F7, 1F11, and 2B6) generated previously exhibited cluster-specific binding effects. Combining sequence alignment and blocking immune epitopes, we sequentially designed a total of 18 mutant proteins containing one, two, or three mutations, or swapped regions. Indirect enzyme-linked immunosorbent assay (ELISA) demonstrated that the three blocking mAbs lost or showed significantly reduced binding for H383Y, D387N, V390D, and T391D mutant proteins. Combining data from mutant proteins with swapping regions and point mutations, the binding region of the three mAbs was mapped to residues 380-395. Sequence alignment of this region showed within-cluster conservation and between-cluster variations, further strengthening the idea of blockade epitope-mediated evolution of NoV.
诺如病毒（NoV）是全球范围内导致急性病毒性肠胃炎的主要病原体。除了偶尔爆发外，还主要报告了散发性 GII.6 NoV 病例。我们使用源自三个不同簇的 GII.6 NoV 的主要衣壳蛋白 VP1，证明了先前产生的三种阻断单克隆抗体（mAbs，1F7、1F11 和 2B6）表现出簇特异性结合效应。通过序列比对和阻断免疫表位，我们依次设计了总共 18 种突变蛋白，包含一个、两个或三个突变或交换区域。间接酶联免疫吸附试验（ELISA）表明，三种阻断 mAb 对 H383Y、D387N、V390D 和 T391D 突变蛋白的结合失去或显著降低。将突变蛋白与交换区域和点突变的数据结合起来，三个 mAb 的结合区域被映射到残基 380-395。该区域的序列比对显示了簇内保守性和簇间变异，进一步加强了 NoV 阻断表位介导的进化思想。
