Here is an introduction video about Zika Virus from the CDC:

Introduction to Zika and Lysosomal Activation

Stakeholders involved
Viruses transmitted from mother to fetus can cause severe damage to the developing brain. Among the most threatening of viruses to the developing brain, Zika is a mosquito-borne, positive-stranded RNA virus that was originally isolated in Uganda and spread to cause epidemics in Africa, Asia, and the Americas. Evidence has shown that in the Americas, the virus caused microcephaly, congenital Zika syndrome, and a multitude of neurodevelopmental disorders. In 2016, the World Health Organization declared Zika a Public Health Emergency of International Concern. Despite an ongoing international investigation of how Zika impacts the developing brain, there is currently no preventative treatment or cure for the virus. However, a growing understanding of lysosomal function suggests that lysosomal activation could enhance a cell’s ability to eradicate viruses like Zika. Lysosomes play a significant role in autophagy, immune functions, and cellular signaling. Consequently, lysosomal dysfunction can impair maintenance of cellular health. Ongoing work is evaluating use of lysosomal modulations in treating autoimmune diseases, neurodegenerative disorders, and cancer. Preliminary data suggest that lysosomal activation is required for inhibiting viral replication and promoting neuronal survival. These data have opened a potential avenue for viral inhibition through lysosomal activation therapy. 
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Perera, R. M., & Zoncu, R. (2016). The Lysosome as a Regulatory Hub. Annual review of cell and developmental biology, 32, 223–253. https://doi.org/10.1146/annurev-cellbio-111315-125125 
​Bonam, S. R., Wang, F., & Muller, S. (2019). Lysosomes as a therapeutic target. Nature reviews. Drug discovery, 18(12), 923–948. https://doi.org/10.1038/s41573-019-0036-1 

  1. Children prenatally infected with Zika and their families
  2. Obstetricians, neurologists, other health providers
  3. Virologists investigating the autophagy pathway 
  4. Pharmaceutical companies
  5. Government health agencies impacted by Zika epidemics
  6. People living in areas affected by mosquito-borne illnesses

Our Hypothesis


  Modifying Cellular Degradation will Prevent Virally Induced Brain Injury 

Methodology

Team VIRAL will test our hypothesis with four different drugs, either autophagy activators or inhibitors, that each act on a different part of the lysosomal autophagy pathway. These are PD146176, Trehalose, Metformin, and Chloroquine. To test our drugs, we are using an immunocompetent mouse model system design that mirrors the human condition. We first infect our pregnant mice at a time point that correlates with the first trimester in humans. We will then treat the mice with one of the four drugs we outlined earlier or a control treatment.  From there, we will do analysis including motor and social development tests, weight measurement, cell density analysis and brain measurements. This approach allows us to effectively compare the extent, severity and location of injury between our different treatments and experimental groups. 
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Research Approach

Team VIRAL has outlined four different experiments. We are currently working on experiment 1, where we are investigating which of our four drugs will increase survival of the infected pups. In future experiments 2-4, we hope to look at optimal dosages, each drug’s effect on preventing microcephaly, and each drug’s safety.