Alignment of Alzheimer's Disease Amyloid-β Peptide and Herpes Simplex Virus-1 pUL15 C-Terminal Nuclease Domain

Abstract

The cause of Alzheimer's disease (AD) is poorly understood. Neurotropic microbes, particularly herpesviruses, might set off chronic neuroinflammation. Amyloid-β (Aβ) has antimicrobial properties and could represent a brain defense against infection. Objective: We searched for protein sequence alignment between herpes simplex virus type I (HSV-1) HSV-2, and Aβ. Methods: Protein data bank (pdb) structures for Aβ, HSV-1, and HSV-2 were searched on the RCSB Protein Data Bank. The protein structures were superimposed and aligned on PYMOL v 2.3.4. Results: For HSV-1 and Aβ, amino acid residues ser549 - his569 of HSV-1 aligned closely with residues asp7 - asn27 of Aβ. For HSV-2 and Aβ, amino acid residues of HSV-2 aligned less closely than those of HSV-1 with residues of Aβ. Conclusion: Conjugating and binding to the same alpha helix in the HSV-1 protease, Aβ could be marking HSV-1 for attack by the immune system, providing a rapid inherited immune response to a destructive neurotropic virus that would otherwise require the more time-consuming involvement of T-cells, B-cells, and the adaptive immune system. But older people do not respond to viral infections as well as younger individuals. When HSV-1 infection advances in an old person, more and more amyloid is produced, forming an adhesive web. As the brain tries to hold the pathologic process in check, neuroinflammation increases and spreads. Progressive neurodegeneration and cognitive decline are the outcome.