About This Project

The WHO recently declared Zika virus a public health emergency of international concern, due to its association with microcephaly, a devastating brain abnormality of newborn children. There are currently no treatments or vaccines available for Zika. We seek to develop an ethical mouse model of Zika virus infection and disease that can be used to test new treatments and vaccines; an essential test system to ensure that only those interventions that actually work proceed into human studies.

Ask the Scientists

What is the context of this research?

On 1 Feb 2016, the WHO declared the recent Zika virus outbreak a public health emergency of international concern after >4500 children were born with foetal brain abnormalities including microcephaly. These cases have occurred primarily in Brazil and in resource poor environments, with the children likely to require extensive help and care for most of their lives. Current data suggests only about 1% of mothers infected during pregnancy are likely to deliver a child with brain abnormalities; however, the high infection rate has resulted in so many cases (Lancet article http://dx.doi.org/10.1016/S0140-6736(16)00651-6 ).

What is the significance of this project?

There are currently no treatments or vaccines for Zika. An essential tool for the scientific and biotechnology community to develop new treatments or vaccines for Zika is an animal model in which such new interventions can be tested. Only drugs/vaccines that work in an animal model can proceed to human testing, leading to further development and ultimately use in human populations.

We propose to develop such a test system for Zika, exploiting our extensive experience with mouse models of arboviral diseases (eg CHIKV; WNV) and panel of genetically modified mice (eg. GMO mice). A lethal model of Zika has recently been published (Dowall et al.2016), however, lethal models are ethically discouraged as they cause excessive suffering and do not recapitulate human disease.

What are the goals of the project?

We seek to infected with Zika virus a series of mice that are deficient in various anti-viral defence genes; specifically genes in the type I interferon pathway comprising IPS-1 deficient mice, IFN response factors 3 and/or 7 deficient mice, and RIG-I deficient mice. Current data suggests wild-type mice will be refractory to infection and mice with complete deletion of the type I interferon pathway will die (Dowall et al.2016). The aforementioned GMO mice all sit at various positions between these two extremes, with partial defects in the type I interferon pathway.

The ideal mouse model is one where 100% of mice are infected, virus can be detected in the blood for 2-3 days, and infection causes limited or no suffering or morbidity (to be monitored by in-house veterinary staff).