Amyloid precursor protein is a restriction factor that protects against Zika virus infection in mammalian brains

Amy Lingel, Haishuang Lin, Yuval Gavriel, Eric Weaver, Pascal Polepole, Virginia Lopez, Yuguo Lei, Thomas M. Petro, Beka Solomon, Chi Zhang, Luwen Zhang

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


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 enhancing 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 neonatalmice resulted in highermortality 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.

Original languageEnglish (US)
Pages (from-to)17114-17127
Number of pages14
JournalJournal of Biological Chemistry
Issue number50
StatePublished - Dec 11 2020

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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