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.
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.
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