RESUMO
Amyloid plaques, the hallmark of Alzheimer's disease (AD), contain fibrillar ß-amyloid (Aß) 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. Aß 1-40 and Aß 1-42 display anti-bacterial, anti-yeast and anti-viral activities. Here, fibroblast, epithelial and neuronal cell lines were exposed to Aß 1-40 or Aß 1-42 and challenged with HSV-1. Quantitative analysis revealed that Aß 1-40 and Aß 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, Aß 1-40 and Aß 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 Aß 1-40 and Aß 1-42 acted directly on HSV-1 in a cell-free system and prevented viral entry into cells. The sequence homology between Aß and a proximal transmembrane region of HSV-1 glycoprotein B suggested that Aß interference with HSV-1 replication could involve its insertion into the HSV-1 envelope. Our data suggest that Aß peptides represent a novel class of antimicrobial peptides that protect against neurotropic enveloped virus infections such as HSV-1. Overproduction of Aß 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.
