Severity of 2015 Outbreak Fuels ResearchZika virus (ZIKV) is a flavivirus transmitted primarily through mosquito bites. It was first discovered in 1947, and outbreaks described from the 1960s through 1980s were associated with mild illness in affected humans. A Brazilian outbreak in 2015, however, has been associated with Guillain-Barré syndrome and other neurological disorders in infected humans, along with fetal abnormalities such as stillbirth and microcephaly.
As of today, the outbreak has spread to other countries, including the United States.
Control efforts have focused primarily on the mosquito vectors, Aedes aegypti and Aedes albopictus, and prevention of mosquito bites. As there are no specific treatments available for Zika, significant scientific resources are currently focused on ZIKV research.
Existing Animal Models Slow ZIKV ResearchZIKV research encompasses different aims, from understanding the progression of the disease, including in pregnancy, through testing vaccines and antiviral drugs. A suitable animal model is critical to understanding this disease and developing treatments.
Since 2015, several animal models have been used for ZIKV studies, including:
This heavy reliance on NHP and genetically engineered animal models not only increases the cost of research, but raises possible issues with the translatability. Insights from studies conducted on immunocompromised, genetically engineered mouse models of Zika virus may not apply to immunocompetent humans of the disease.
- Rhesus macaques
- Immunocompromised Ifnar1 knockout (A129) and Ifnar1/Ifngr1 double knockout (AG129) mice
- Immunocompromised Irf3/Irf5/Irf7 triple knockout mice
- Pregnant SJL mice
A more affordable and translatable mouse model of Zika pathology would accelerate the development of treatment options, but our most frequently used biomedical research models proved resistant to infection.
A New Mouse Model of Zika Virus InfectionC57BL/6 mice, the most commonly used inbred strain in biomedical research, have previously been reported as resistant to ZIKV. FDA researchers recently discovered a means of bypassing this resistance, establishing an immunocompetent b6 mouse model of Zika pathology for further investigation.
Their study demonstrates a neonatal infection method which results in CNS infection and neurologic symptoms. According to the authors, "This model does not address transplacental transmission of virus from mother to fetus or adult transmission, however it offers an immunocompetent symptomatic mouse model for ZIKV infections that may prove useful to understand the long term effects of ZIKV infection."
|Symptoms||B6 WT||IFNAR KO|
|Bilateral flaccid hind limb paralysis||-||++|
Note: Above table adapted from PLoS Pathog. 12(11):e1006004.
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