About This Project

Antibody Dependent Enhancement maybe involved in the spread of Zika. We are interested in characterizing Zika NS1 protein and seeing if Zika NS1 binds to IgG antibody immune complexes and if this binding can be inhibited. Next we want to characterize African Zika NS1 and Asian Zika NS1 proteins to see if the Asian Zika NS1 binds IgG antibody immune complexes with a higher avidity than African Zika NS1. Changes in Asian Zika NS1 protein, may be fueling the spread of Zika in the Americas.

Ask the Scientists

What is the context of this research?

The Aedes mosquitoes spreading Zika are poor vectors of Zika, suggesting that other factors may be contributing to the explosive spread of Zika in the Americas. Scott Halstead MD believes this may be due to Antibody Dependent Enhancement (ADE) of infection. This is where viruses such as dengue or Zika use our antibodies against us. We previously identified a viral protein receptor we found in dengue which contributes to the spread and severity of dengue. Inhibition of this viral protein, both cell culture (in vitro) and in animals (in vivo) lead to an issued US patent for treating dengue/DHF/DSS (US patent 8,815,813).

What is the significance of this project?

Zika and dengue are both Flaviviridae and are very closely related. Antibodies to previous dengue infections often cross-react with the Zika virus and may contribute to the spread of Zika. These cross-reactive, antibodies are associated with ADE. ADE is thought to contribute to the spread and severity of dengue infections and we believe the same phenomenon may be contributing to the spread of Zika. It is known that there are genetic changes in the African and Asian Zika NS1 proteins, but the significance of these changes is not known. We want to measure whether the Asian Zika NS1 protein binds with a higher avidity to antibodies. The Zika strain spreading through the Americas is the Asian strain and it has been reported that the Asian strain is more pathogenic than the African strain.

What are the goals of the project?

We want to characterize whether different strains of Zika NS1 protein bind to antibodies differently and if this binding can be inhibited. We believe the viral proteins we have found in dengue and Ebola contribute to the spread and severity of these viruses and we want to see if this is also true for Zika. We have found that inhibition of these viral receptors resulted in higher in vivo survival in a mouse model of ADE in dengue and may help reduce the spread and severity of Zika. We have shown that myelin basic protein also binds IgG IC and this interaction may contribute to autoimmunity. Guillain-Barré syndrome(GBS) is an autoimmune disease that can be triggered by recent Zika infections. Inhibition of these viral proteins may help treat GBS.