title: Alzheimer's associated β-amyloid protein inhibits influenza A virus and modulates viral interactions with phagocytes.
abstract: Accumulation of β-Amyloid (βA) is a key pathogenetic factor in Alzheimer's disease; however, the normal function of βA is unknown. Recent studies have shown that βA can inhibit growth of bacteria and fungi. In this paper we show that βA also inhibits replication of seasonal and pandemic strains of H3N2 and H1N1 influenza A virus (IAV) in vitro. The 42 amino acid fragment of βA (βA42) had greater activity than the 40 amino acid fragment. Direct incubation of the virus with βA42 was needed to achieve optimal inhibition. Using quantitative PCR assays βA42 was shown to reduce viral uptake by epithelial cells after 45 minutes and to reduce supernatant virus at 24 hours post infection. βA42 caused aggregation of IAV particles as detected by light transmission assays and electron and confocal microscopy. βA42 did not stimulate neutrophil H2O2 production or extracellular trap formation on its own, but it increased both responses stimulated by IAV. In addition, βA42 increased uptake of IAV by neutrophils. βA42 reduced viral protein synthesis in monocytes and reduced IAV-induced interleukin-6 production by these cells. Hence, we demonstrate for the first time that βA has antiviral activity and modulates viral interactions with phagocytes.
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Mitchell R
authors.initials: MR
authors.lastname: White
authors.affiliation: Hebrew Senior Life, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Ruth
authors.initials: R
authors.lastname: Kandel
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Shweta
authors.initials: S
authors.lastname: Tripathi
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Condon
authors.affiliation: National Institute of Allergy and Infectious Disease, Bethesda, Maryland, United States of America.
authors.forename: Li
authors.initials: L
authors.lastname: Qi
authors.affiliation: National Institute of Allergy and Infectious Disease, Bethesda, Maryland, United States of America.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Taubenberger
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Kevan L
authors.initials: KL
authors.lastname: Hartshorn
mesh_terms: D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D000998:Antiviral Agents / Q000276:immunology*; D002460:Cell Line; D054884:Host-Pathogen Interactions; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology / Q000502:physiology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology / Q000502:physiology; D009980:Influenza A virus / Q000276:immunology / Q000502:physiology*; D007251:Influenza, Human / Q000276:immunology*; D009000:Monocytes / Q000276:immunology / Q000821:virology; D009504:Neutrophils / Q000276:immunology / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology*; D010586:Phagocytes / Q000276:immunology / Q000821:virology*
chemical_list: D016229:Amyloid beta-Peptides; D000998:Antiviral Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)