β-Amyloid peptides display protective activity against the human Alzheimer's disease-associated herpes simplex virus-1.
Amyloid plaques, the hallmark of Alzheimer's disease (AD), contain fibrillar β-amyloid (Aβ) 1-40 and 1-42 peptides. Herpes simplex virus 1 (HSV-1) has been implicated as a risk factor for AD and found to co-localize within amyloid plaques. Aβ 1-40 and Aβ 1-42 display anti-bacterial, anti-yeast and anti-viral activities. Here, fibroblast, epithelial and neuronal cell lines were exposed to Aβ 1-40 or Aβ 1-42 and challenged with HSV-1. Quantitative analysis revealed that Aβ 1-40 and Aβ 1-42 inhibited HSV-1 replication when added 2 h prior to or concomitantly with virus challenge, but not when added 2 or 6 h after virus addition. In contrast, Aβ 1-40 and Aβ 1-42 did not prevent replication of the non-enveloped human adenovirus. In comparison, antimicrobial peptide LL-37 prevented HSV-1 infection independently of its sequence of addition. Our findings showed also that Aβ 1-40 and Aβ 1-42 acted directly on HSV-1 in a cell-free system and prevented viral entry into cells. The sequence homology between Aβ and a proximal transmembrane region of HSV-1 glycoprotein B suggested that Aβ interference with HSV-1 replication could involve its insertion into the HSV-1 envelope. Our data suggest that Aβ peptides represent a novel class of antimicrobial peptides that protect against neurotropic enveloped virus infections such as HSV-1. Overproduction of Aβ peptide to protect against latent herpes viruses and eventually against other infections, may contribute to amyloid plaque formation, and partially explain why brain infections play a pathogenic role in the progression of the sporadic form of AD.
Research Center on Aging, Graduate Program in Immunology, Faculty of Medicine and Health Sciences, University of Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC, J1H 5N4, Canada.
Karine
K
Bourgade
Hugo
H
Garneau
Geneviève
G
Giroux
Aurélie Y
AY
Le Page
Christian
C
Bocti
Gilles
G
Dupuis
Eric H
EH
Frost
Tamàs
T
Fülöp
D000544:Alzheimer Disease / Q000453:epidemiology / Q000821:virology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology / Q000821:virology; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology / Q000821:virology; D006561:Herpes Simplex / Q000517:prevention & control; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology / Q000821:virology; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D058225:Plaque, Amyloid / Q000821:virology; D012307:Risk Factors; D014779:Virus Replication / Q000187:drug effects*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments