A Mouse Model of Zika Virus Pathogenesis
Open accessAbstract
The ongoing Zika virus (ZIKV) epidemic and unexpected clinical outcomes, including Guillain-Barré syndrome and birth defects, has brought an urgent need for animal models. We evaluated infection and pathogenesis with contemporary and historical ZIKV strains in immunocompetent mice and mice lacking components of the antiviral response. Four- to six-week-old Irf3(-/-)Irf5(-/-)Irf7(-/-) triple knockout mice, which produce little interferon α/β, and mice lacking the interferon receptor (Ifnar1(-/-)) developed neurological disease and succumbed to ZIKV infection, whereas single Irf3(-/-), Irf5(-/-), and Mavs(-/-) knockout mice exhibited no overt illness. Ifnar1(-/-) mice sustained high viral loads in the brain and spinal cord, consistent with evidence that ZIKV causes neurodevelopmental defects in human fetuses. The testes of Ifnar1(-/-) mice had the highest viral loads, which is relevant to sexual transmission of ZIKV. This model of ZIKV pathogenesis will be valuable for evaluating vaccines and therapeutics as well as understanding disease pathogenesis.
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AG129 and Irf3/5/7 TKO mice have been indicated to be uncommonly available in some research laboratories.
“Furthermore, AG129 and Irf3/5/7 TKO mice has been indicated to be uncommonly available in some research laboratories [33, 34].”
From ICR suckling mouse model of Zika virus infection for disease modeling and drug validation (2018) · cites this paper as [34]
The Experimental Procedures (Mouse experiments; page not provided) list AG129 and Irf3/5/7 TKO mice among the strains used and say the mice were bred at Washington University or, for WT and CD-1 mice, purchased. Neither that passage nor the Results passages address how commonly these strains are available in other research laboratories. Searched for availability and whether the strains are widely available. (LLM, conf=0.76)
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Broadly Neutralizing Activity of Zika Virus-Immune Sera Identifies a Single Viral Serotype
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Overview on the Current Status of Zika Virus Pathogenesis and Animal Related Research
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- Authors
- Lazear, H. M., Govero, J., Smith, A. M., Platt, D. J., Fernandez, E., Miner, J. J., & Diamond, M. S.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Washington University in St. Louis (US)
- Corresponding author
- Diamond, Michael S.
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 19
- Issue
- 5
- Pages
- 720-730
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC4866885
- OpenAlex
- W2327959547
- Cited by
- 909
- References
- 68
- Citations by year
- 2026: 28 · 2025: 40 · 2024: 44 · 2023: 52 · 2022: 51 · 2021: 81 · 2020: 94 · 2019: 118 · 2018: 128 · 2017: 167 · 2016: 105
- FWCI
- 171.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Rheumatology Research Foundation
- National Institutes of Health (AI073755, R01 AI073755)
- National Human Genome Research Institute (R25HG006687)
- National Institute of Allergy and Infectious Diseases (R01AI073755, R01AI104972, T32AI007163)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Vectors
- Keywords
- Zika virus, mouse model, interferon signaling, IRF3, IRF5, IRF7, IFNAR1, MAVS, neurodevelopmental defects, Guillain-Barré syndrome, sexual transmission, antiviral response
- MeSH terms
- Zika Virus Infection, Zika Virus, Animals, Chlorocebus aethiops, Disease Models, Animal, Humans, Male, Mice, Inbred C57BL, Vero Cells, Mice, Knockout, Mice
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