Background: Human herpes viruses (HHV) have been implicated in dementia. Class II Human Leukocyte Antigens (HLA) play a critical role in host protection from foreign antigens including herpes viruses through stimulating antibody production against them. In the present study we investigated the in silico binding affinity of 9 H HV to three Class II HLA alleles that have been found to protect against dementia: DRB1*01:01, DRB1*13:02, and DRB1*15:01. Methods: 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. Findings: 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. Interpretation: 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.
Bibliographical noteFunding Information:
Partial funding for this study was provided by the University of Minnesota (the Kunin Professorship for Women's Healthy Brain Aging, the Brain and Genomics Fund, and the McKnight Presidential Chair of Cognitive Neuroscience), the American Legion Brain Sciences Chair, and the United States Department of Veterans Affairs. The sponsors had no role in the current study design, analysis or interpretation, or in the writing of this paper. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government.
- Human herpes virus
- Human leukocyte antigen (HLA)
- Sturniolo method
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, Non-P.H.S.