Honors Program


Date of this Version


Document Type



Villarreal, D. Zhang, L. 2021. Protein Related to Alzheimer's Disease Plays a Role in Zika Virus Infection. Undergraduate Honors Thesis. University of Nebraska - Lincoln.


Copyright Delaney Villarreal and Luwen Zhang 2021.


Zika virus (ZIKV) is a neurotropic flavivirus, infection by which can lead to microcephaly in babies and Guillain-Barre syndrome in adults. Flaviviruses are single-stranded RNA viruses, including West Nile virus and Dengue virus. Amyloid Precursor Protein (APP) is a membrane protein associated with the development of Alzheimer’s disease through its involvement in the generation of amyloid plaques. APP is predominantly expressed in the brain and has restricted expression in other organs, so the roles it may play outside the brain are not fully understood. Although there is plenty of research on ZIKV, there is no clinically approved treatment or vaccine for ZIKV-mediated diseases. There is limited knowledge regarding what host factors ZIKV interacts with to modulate the progression of the disease. The spleen is the organ of the body dedicated to filtering the blood, removing old and damaged blood cells. As part of the lymphatic system, it plays a crucial role in mounting an immune response to bacterial or viral infections. In the spleen, the level of APP expression is usually low. We have demonstrated that ZIKV infection in mice causes the upregulation of APP protein in the spleen. Additionally, we observed that cells expressing APP have more protection against ZIKV and provide protection for other surrounding cells. The overexpression of APP in the spleen may play an important role for the host to counteract ZIKV-mediated pathogenesis. We are currently working to ascertain the exact role of APP, its induction mechanism, and how this expression influences ZIKV replication using a genetic approach. This work may provide novel information about host-viral interaction and a potential target for anti-ZIKV treatment. It also could provide information about ZIKV and the development of Alzheimer’s, with both being linked to APP expression.