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The recent Zika epidemics have exposed gaps in our knowledge about the virus and interventions to manage and prevent infection. An animal model could help to answer some questions. Investigators at the University of Texas Medical Branch, after finding that injecting immunocompetent mice subcutaneously with Zika virus (ZIKV) did not lead to signs of illness or viremia, injected ZIKV into mice (A129) that lack the interferon alpha receptor. They also injected virus into mice that lacked both type I and type II interferon responses (AG129). The ZIKV used was an Asian lineage from a sick child in Cambodia in 2010.
The immunodeficient mice inoculated with ZIKV subcutaneously developed signs of illness (tremors, anorexia, weight loss); severity was age-related, with all mice infected at 3 weeks old being moribund by day 6 postinoculation. Viremia peaked on day 2 postinoculation and was found in the brain by day 3. All AG129 mice showed signs of neurological disease by day 6. Mice that were older at inoculation became ill and were viremic but recovered. In euthanized mice, virus was found in all organs, with replication mainly in the spleen, testes, and brain.
Rossi SL et al. Characterization of a novel murine model to study Zika virus. Am J Trop Med Hyg 2016 Mar 28; [e-pub]. (http://dx.doi.org/10.4269/ajtmh.16-0111)
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The authors note that the mouse model may not be useful in defining pathogenesis of Zika infections but may be valuable for screening antiviral compounds and for testing candidate vaccines. An animal model also would be important in supporting causality of Zika virus infection and brain defects in the fetus. Notable also was the finding that the virus replicated to high levels in the testes of male mice, given reports of sexual transmission in humans in the recent outbreak. The authors discuss a possible protective role of interferon in Zika infections.