Date of this Version
Bunz, Jacob. (2021) Zika Virus Systematic Induction: Amyloid Precursor Protein as Restriction Factor in Lungs. Nebraska Center for Virology, University of Nebraska-Lincoln.
For many years the neurotic flavivirus, the Zika Virus (ZIKV), has been studied to determine its role in causing birth defects in humans. Such defects can include microcephaly and other severe brain defects. One of the defenses against viruses of this kind is intrinsic immunity, which defends against viruses with the use of host anti-viral restriction factors. Today, there is still little knowledge on the intrinsic immunity against ZIKV in the body. For this experiment precisely, this topic was explored using lung tissue as a control to study the systematic induction of ZIKV. This builds off prior ZIKV intrinsic immunity research conducted on brain and blood tissue. Amyloid precursor protein (APP) is a protein that is primarily expressed in brains and is also involved in the pathogenesis of Alzheimer's disease. It was found that ZIKV interacts with APP because there is an increase in APP expression when ZIKV is introduced into APP-containing tissue. This occurs because APP stability is enhanced when interacting with ZIKV, which is reflected in a higher expression. There are several findings found during this research that suggest APP is a restriction factor that actively protects against ZIKV by functioning as a decoy receptor and that it serves a protective role in brain injuries mediated by ZIKV. One finding showed that aging brain tissues containing APP possessed protective effects against ZIKV infection by reducing the availability of the viruses. Another observation showed us that ZIKV replication in human neural stem cells was greatly enhanced when less APP expression was allowed or when APP-ZIKV interactions were blocked. Finally, another finding showed that the intracranial infection of ZIKV in APP-null neonatal lab mice resulted in a significantly higher mortality rate and viral yield.