IITRI will be presenting at the upcoming International Meeting on Emerging Diseases and Surveillance (IMED) November 4-7, 2016 in Vienna, Austria, on Zika Mouse and Macque Models developed by our Molecular and Microbiology team. For more details, please contact us.
Authors: D. Boltz1, P. Curry,1, R. Baker2; 1IIT Research Institute, MMB, Chicago/US, 2IIT Research Institute, MMB, Chicago, IL/US
Title: Development of Models for Zika Virus Infection in Mice and Rhesus Macaques Using a Contemporary Virus Strain
Purpose: Zika virus is a zoonotic pathogen that recently emerged in North and South America. Zika virus infections in humans can cause severe birth defects. There is an urgent need for animal models to study viral pathogenesis and to test vaccine and therapeutic medical countermeasures against this imprtant pathogen.
Methods & Materials: Zika virus strain PRVABC59 was used for all studies in this project. For mouse studies, AG129 mice were infected with various doses of Zika virus via the subcutaneous route. For NHP studies, sexually-mature male Eighteen Rhesus macaques were infected with 1×104 PFU of Zika virus via the subcutaneous route. Animals were monitored for clinical signs including weight loss, rash, body temperature, and survival, as well as viral load in blood samples, oral swabs and semen samples (NHPs). Methods for the electro ejaculation of NHPs were developed for the collection of semen samples.
Results: AG129 were found to be extremely susceptible to infection with Zika virus. The LD50 was found to be less than 100 PFU, with mice exhibiting a dose-dependent hange in the mean time to death. Mice showed few clinical signs until a few days before death, at which point the exhibited severe weight loss and hypothermia. Rhesus macaques exhibited few slinical signs of infection, much like humans. There was equivocal observations of rash on a few animals, but no observed change in body weight, body temperature or activity levels. However, viral genomes were easily detected by qRT-PCR extracts of blood samples for as much as a week after infection. Viral load was also assessed in oral swabs and in semen samples for up to two months after infection.
Conclusion: We conclude that the lethal AG129 mouse model is likely a useful model for early screening of medical countermeasures against Zika virus infection, especially for therapeutics and provides very clear endpoints in a less-expensive model. The mouse model may be less useful for vaccine and immunomodulatory drug testing due to the Type I and II interferon receptor knockout background in these mice. The Rhesus macaque model likely mimics the human disease more closely, but suffers from less clear endpoints and higher costs.