Alzheimer's Associated beta-Amyloid Protein Inhibits Influenza A Virus and Modulates Viral Interactions with Phagocytes

作者：White Mitchell R; Kandel Ruth; Tripathi Shweta; Condon David; Qi Li; Taubenberger Jeffrey; Hartshorn Kevan L^*

来源：PLos One, 2014, 9(7): e101364.

DOI：10.1371/journal.pone.0101364

Accumulation of beta-Amyloid (beta A) is a key pathogenetic factor in Alzheimer's disease; however, the normal function of beta A is unknown. Recent studies have shown that beta A can inhibit growth of bacteria and fungi. In this paper we show that beta A also inhibits replication of seasonal and pandemic strains of H3N2 and H1N1 influenza A virus (IAV) in vitro. The 42 amino acid fragment of beta A (beta A42) had greater activity than the 40 amino acid fragment. Direct incubation of the virus with beta A42 was needed to achieve optimal inhibition. Using quantitative PCR assays beta A42 was shown to reduce viral uptake by epithelial cells after 45 minutes and to reduce supernatant virus at 24 hours post infection. beta A42 caused aggregation of IAV particles as detected by light transmission assays and electron and confocal microscopy. beta A42 did not stimulate neutrophil H2O2 production or extracellular trap formation on its own, but it increased both responses stimulated by IAV. In addition, beta A42 increased uptake of IAV by neutrophils. beta A42 reduced viral protein synthesis in monocytes and reduced IAV-induced interleukin-6 production by these cells. Hence, we demonstrate for the first time that beta A has antiviral activity and modulates viral interactions with phagocytes.

• 出版日期2014-7-2