A sliding window approach was used to partition the amino acid sequences of surface glycoproteins from HHV 1-8 into subsequences. The binding affinity of the HHV subsequences to Class II HLA surface receptor proteins was predicted using the Sturniolo method in the Immune Epitope Database and reported as a percentile rank. The binding affinity of HHV subsequences to protective alleles was compared to that of three dementia-neutral Class II HLA alleles: DRB1*03:01, DRB1*07:01, and DRB1*08:01.
Binding affinity varied widely for each HLA allele, HHV type, and HHV subsequence. The protective alleles had significantly higher binding affinity that than the neutral alleles. The largest differences in binding affinity between the protective and neutral alleles was shown for HHV-6A and HHV-6B, which had the best overall binding affinity with the protective alleles.
The dementia protection conferred by the three protective HLA alleles investigated here is related to their superior ability to bind and successfully eliminate HHV epitopes - in particular, HHV6 - that could otherwise cause dementia if they persisted.
使用滑动窗口方法将来自HHV1-8的表面糖蛋白的氨基酸序列划分为子序列。使用免疫表位数据库中的Sturniolo方法预测HHV子序列与II类HLA表面受体蛋白的结合亲和力,并报告为百分位数排名。将HHV子序列与保护性等位基因的结合亲和力与三个痴呆中性II类HLA等位基因的结合亲和力进行了比较:DRB1*03:01,DRB1*07:01和DRB1*08:01。
每个HLA等位基因的结合亲和力差异很大,HHV型,和HHV子序列。保护性等位基因的结合亲和力明显高于中性等位基因。HHV-6A和HHV-6B显示了保护性和中性等位基因之间结合亲和力的最大差异,与保护性等位基因具有最佳的整体结合亲和力。
本文研究的三个保护性HLA等位基因赋予的痴呆保护作用与它们结合并成功消除HHV表位的优越能力有关-特别是,HHV6-如果持续存在,可能会导致痴呆症。