Amyloid precursor protein is a restriction factor that protects against Zika virus infection in mammalian brains
Autor: | Thomas M. Petro, Amy Lingel, Beka Solomon, Yuval Gavriel, Haishuang Lin, Yuguo Lei, Virginia Lopez, Pascal Polepole, Chi Zhang, Luwen Zhang, Eric A. Weaver |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Intrinsic immunity Virus Replication Microbiology Biochemistry Zika virus Amyloid beta-Protein Precursor Mice 03 medical and health sciences Neural Stem Cells Interferon mental disorders Amyloid precursor protein medicine Animals Humans Aging brain Molecular Biology Mice Knockout Gene knockdown Innate immune system 030102 biochemistry & molecular biology biology Zika Virus Infection Brain Zika Virus Cell Biology biology.organism_classification Virology Flavivirus 030104 developmental biology Gene Expression Regulation biology.protein medicine.drug |
Zdroj: | J Biol Chem |
ISSN: | 0021-9258 |
Popis: | Zika virus (ZIKV) is a neurotropic flavivirus that causes several diseases including birth defects such as microcephaly. Intrinsic immunity is known to be a frontline defense against viruses through host anti-viral restriction factors. Limited knowledge is available on intrinsic immunity against ZIKV in brains. Amyloid precursor protein (APP) is predominantly expressed in brains and implicated in the pathogenesis of Alzheimer's diseases. We have found that ZIKV interacts with APP, and viral infection increases APP expression via enhancing protein stability. Moreover, we identified the viral peptide, HGSQHSGMIVNDTGHETDENRAKVEITPNSPRAEATLGGFGSLGL, which is capable of en-hancing APP expression. We observed that aging brain tissues with APP had protective effects on ZIKV infection by reducing the availability of the viruses. Also, knockdown of APP expression or blocking ZIKV-APP interactions enhanced ZIKV replication in human neural progenitor/stem cells. Finally, intracranial infection of ZIKV in APP-null neonatal mice resulted in higher mortality and viral yields. Taken together, these findings suggest that APP is a restriction factor that protects against ZIKV by serving as a decoy receptor, and plays a protective role in ZIKV-mediated brain injuries. |
Databáze: | OpenAIRE |
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