title: Protective Effect of Amyloid-β Peptides Against Herpes Simplex Virus-1 Infection in a Neuronal Cell Culture Model.
abstract: Senile amyloid plaques are one of the main hallmarks of Alzheimer's disease (AD). They correspond to insoluble deposits of amyloid-β peptides (Aβ) and are responsible for the inflammatory response and neurodegeneration that lead to loss of memory. Recent data suggest that Aβ possess antimicrobial and anti-viral activity in vitro. Here, we have used cocultures of neuroglioma (H4) and glioblastoma (U118-MG) cells as a minimal in vitro model to investigate whether Aβ is produced by neuroglioma cells and whether this could result in protective anti-viral activity against HSV-1 infection. Results showed that H4 cells secreted Aβ42 in response to HSV-1 challenge and that U118-MG cells could rapidly internalize Aβ42. Production of pro-inflammatory cytokines TNFα and IL-1β by H4 and U118-MG cells occurred under basal conditions but infection of the cells with HSV-1 did not significantly upregulate production. Both cell lines produced low levels of IFNα. However, extraneous Aβ42 induced strong production of these cytokines. A combination of Aβ42 and HSV-1 induced production of pro-inflammatory cytokines TNFα and IL-1β, and IFNα in the cell lines. The reported anti-viral protection of Aβ42 was revealed in transfer experiments involving conditioned medium (CM) of HSV-1-infected H4 cells. CM conferred Aβ-dependent protection against HSV-1 replication in de novo cultures of H4 cells challenged with HSV-1. Type 1 interferons did not play a role in these assays. Our data established that H4 neuroglioma cells produced Aβ42 in response to HSV-1 infection thus inhibiting secondary replication. This mechanism may play a role in the etiology of AD.
authors.affiliation: Research Center on Aging, Graduate Program in Immunology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Karine
authors.initials: K
authors.lastname: Bourgade
authors.affiliation: Research Center on Aging, Graduate Program in Immunology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Le Page
authors.affiliation: Department of Medicine, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Bocti
authors.affiliation: Department of Pathophysiology, Medical University of Gdansk, Poland.
authors.forename: Jacek M
authors.initials: JM
authors.lastname: Witkowski
authors.affiliation: Department of Biochemistry, Graduate Program in Immunology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Gilles
authors.initials: G
authors.lastname: Dupuis
authors.affiliation: Department of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Eric H
authors.initials: EH
authors.lastname: Frost
authors.affiliation: Department of Medicine, Research Center on Aging, Graduate Program in Immunology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Tamás
authors.initials: T
authors.lastname: Fülöp
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D006561:Herpes Simplex / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism* / Q000821:virology; D009474:Neurons / Q000378:metabolism* / Q000821:virology; D010446:Peptide Fragments / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D017077:Culture Media, Conditioned; C508585:IL1B protein, human; D016898:Interferon-alpha; D053583:Interleukin-1beta; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D053829:Amyloid Precursor Protein Secretases
keywords: Alzheimer’s disease; amyloid-β peptides; cocultures; glial cells; herpes simplex virus-1 (HSV-1); neuronal cells; viral replication inhibition