Format

Send to

Choose Destination
Cell Host Microbe. 2016 May 11;19(5):720-30. doi: 10.1016/j.chom.2016.03.010. Epub 2016 Apr 5.

A Mouse Model of Zika Virus Pathogenesis.

Author information

1
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
2
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
3
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; The Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: diamond@borcim.wustl.edu.

Abstract

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.

PMID:
27066744
PMCID:
PMC4866885
DOI:
10.1016/j.chom.2016.03.010
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center