About This Project

Zika virus is spreading rapidly in the Western hemisphere and is linked to fetal microcephaly. We recently found that new Zika virus strains suppress the antiviral response but not the stress response in human epithelial cells. We hope to determine how Zika virus can suppress the antiviral and stress responses in infected human and mouse cortical neurons. Defining how Zika virus modulates these pathways will help identify interactions that can be targeted for antiviral development.

Ask the Scientists

What is the context of this research?

Zika virus is a member of the positive-sense RNA Flaviviridae family. Although Zika infections typically cause mild symptoms, severe neurologic diseases have recently been reported linking the virus to encephalitis, fetal microcephaly and Guillain-Barre syndrome. Although there is growing evidence of virus associated pathologies, most of what is known is based on related viruses. Recent studies using primary and cell line tissue culture indicate that Zika can replicate in multiple cell types. We recently carried out preliminary experiments using monkey and human epithelial cells as well as brain cells of newborn mice. We found Zika grows at different rates and causes different levels of cell damage. We also observed cell-type specific suppression of antiviral but not stress responses.

What is the significance of this project?

The recent Zika outbreaks are caused by a distinct Asian lineage and our knowledge of its biology is limited. Several publications have indicated that Zika can replicate efficiently in human neuronal cells. Our own studies show that Zika can infect and replicate well in brain cells of newborn mice (neonatal cortical neurons). The infected cells actually remain "healthy" for the first 48 hrs of infection but then quickly start to die by 72 hrs after infection. This data is similar to that reported in humans indicating that Zika growth kinetics, susceptibility and responses are comparable in human and mouse cells. Understanding how Zika keeps actively infected neurons alive to produce large amounts of virus until their exhaustion will help us identify novel therapeutic targets.

What are the goals of the project?

Our goals will be to understand how Zika virus strains (old vs new) infect, replicate and evade the host response. We'll test the ability of Zika to replicate and cause damage to neuronal cells. By including old and new strains, we will also be able to identify potential mutations that may account for these effects. We observed Zika was able to shut down antiviral responses but not stress responses in epithelial cells; therefore we'll see if the same thing occurs in Zika-infected neuronal cells. By carrying out our infections with cells that also have reporter-systems, we will try to define how ZIKV actively slows/shuts-off the antiviral response and why it does not do the same with the cell-stress response.