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Biogerontology

, Volume 16, Issue 1, pp 85–98 | Cite as

β-Amyloid peptides display protective activity against the human Alzheimer’s disease-associated herpes simplex virus-1

  • Karine Bourgade
  • Hugo Garneau
  • Geneviève Giroux
  • Aurélie Y. Le Page
  • Christian Bocti
  • Gilles Dupuis
  • Eric H. Frost
  • Tamàs FülöpJr.
Research Article

Abstract

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.

Keywords

Beta-amyloid peptides Herpes simplex virus-1 Human adenovirus type 5 Viral replication inhibition Antimicrobial peptides Alzheimer’s disease 

Notes

Acknowledgments

This work was supported by Grants-in-aid from the Canadian Institute of Health Research (CIHR) (No. 106634), the Université de Sherbrooke, and the Research Center on Aging.

Conflict of interests

None.

Supplementary material

10522_2014_9538_MOESM1_ESM.pdf (118 kb)
Fig. S1. Time-dependent replication of HSV-1 and HAd5 in MRC-5 and A549 cells, respectively. MRC-5 and A549 cells were exposed to (A) HSV-1 or (B) HAd5 using an initial 0.01 ID50 per cell. Viral replication was analyzed by real-time PCR at the indicated times. Data are a combination of 2 independent experiments performed in duplicate and are shown as the mean ± SEM. Cp designates the crossing point which corresponds to the number of qPCR cycles needed to detect fluorescence of each sample. Fig. S2. Sequence homology between Aβ 1-42 and a transmembrane region of HSV-1 gB. Amino acid sequence alignment of Aβ 1-42 and a transmembrane region (positions 713 – 763) of HSV-1 gB using Clustal Omega shareware (http://expasy.org/proteomics). Identical amino acid residues are indicated by vertical lines and amino acids possessing similar properties, by dashed vertical lines. Adapted with permission from Cribbs et al. (Biochemistry, 39 (2000) 5988-5,994). Copyright 2000, American Chemical Society. Supplementary material 1 (PDF 117 kb)
10522_2014_9538_MOESM2_ESM.docx (23 kb)
Supplementary material 2 (DOCX 24 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Karine Bourgade
    • 1
  • Hugo Garneau
    • 1
  • Geneviève Giroux
    • 2
  • Aurélie Y. Le Page
    • 1
  • Christian Bocti
    • 3
  • Gilles Dupuis
    • 4
  • Eric H. Frost
    • 2
  • Tamàs FülöpJr.
    • 1
  1. 1.Research Center on Aging, Graduate Program in Immunology, Faculty of Medicine and Health SciencesUniversity of SherbrookeSherbrookeCanada
  2. 2.Department of Microbiology and Infectious Diseases, Faculty of Medicine and Health SciencesUniversity of SherbrookeSherbrookeCanada
  3. 3.Department of Medicine, Faculty of Medicine and Health SciencesUniversity of SherbrookeSherbrookeCanada
  4. 4.Department of Biochemistry, Graduate Program in Immunology, Faculty of Medicine and Health SciencesUniversity of SherbrookeSherbrookeCanada

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