<i>In Silico</i> Assessment of Binding Affinities of Three Dementia-Protective Human Leukocyte Antigen (HLA) Alleles to Nine Human Herpes Virus Antigens

Abstract

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 HHV 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. Findings: Binding affinity varied widely for each HLA allele, HHV type, and HHV subsequence. For the three HLA alleles investigated here, HHV-6A and HHV-6B had the best overall binding affinity. Interpretation: The dementia protection conferred by the three HLA alleles investigated here is related to their ability to bind and successfully eliminate HHV epitopes – in particular, HHV6 - that could otherwise cause dementia if they persisted. Funding: The University of Minnesota and the United States Department of Veterans Affairs. Declaration of Interests: The authors declare no competing interests.