A Mouse Model of Zika Virus Pathogenesis

Area of Science:

• Virology and Immunology
• Infectious Diseases
• Animal Models of Disease

Background:

• The Zika virus (ZIKV) epidemic highlights the need for effective animal models due to severe clinical outcomes like Guillain-Barré syndrome and birth defects.
• Understanding ZIKV pathogenesis requires models that accurately mimic human disease progression and host-pathogen interactions.

Purpose of the Study:

• To evaluate ZIKV infection and pathogenesis in immunocompetent mice and mice with deficiencies in key antiviral response pathways.
• To identify a suitable animal model for studying ZIKV neurodevelopmental defects and sexual transmission.

Main Methods:

• Infection studies were conducted using contemporary and historical ZIKV strains in various knockout mouse models, including Irf3(-/-)Irf5(-/-)Irf7(-/-) and Ifnar1(-/-) mice.
• Neurological disease, viral loads in different tissues (brain, spinal cord, testes), and survival rates were monitored.
• Comparison of ZIKV susceptibility was made between single knockout mice and triple knockout or interferon receptor knockout mice.

Main Results:

• Mice lacking interferon signaling (Irf3(-/-)Irf5(-/-)Irf7(-/-) and Ifnar1(-/-)) developed severe neurological disease and succumbed to ZIKV infection.
• Ifnar1(-/-) mice exhibited high viral loads in the central nervous system and testes, correlating with human fetal neurodevelopmental defects and ZIKV sexual transmission.
• Single knockout mice (Irf3(-/-), Irf5(-/-), Mavs(-/-)) showed no overt illness, indicating the critical role of interferon pathways in ZIKV control.

Conclusions:

• Mice lacking interferon responses, particularly Ifnar1(-/-) mice, serve as a valuable model for ZIKV pathogenesis, including neurodevelopmental and sexual transmission aspects.
• This model will facilitate the evaluation of ZIKV vaccines and therapeutics.
• The study underscores the importance of the interferon pathway in controlling ZIKV infection.