In silico assessment of binding affinities of three dementia-protective 2 Human Leukocyte Antigen alleles to nine human herpes virus 3 antigens
permalinkCurrent Research in Translational Medicine - 2020-07-02Charonis S, James L, Georgopoulos AP10.1016/j.retram.2020.06.002BackgroundHuman herpes viruses (HHV) have been implicated in dementia. Class II Human Leukocyte Antigens (
Human Leukocyte Antigen) 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
HLAalleles that have been found to protect against dementia: DRB1*01:01, DRB1*13:02, and DRB1*15:01.
MethodsA 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
HLAsurface 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
HLAalleles: DRB1*03:01, DRB1*07:01, and DRB1*08:01.
FindingsBinding affinity varied widely for each
HLAallele, 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.
InterpretationThe dementia protection conferred by the three protective
HLAalleles 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.