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Cell Rep. 2016 Sep 20;16(12):3208-3218. doi: 10.1016/j.celrep.2016.08.079. Epub 2016 Sep 6.

Zika Virus Infection in Mice Causes Panuveitis with Shedding of Virus in Tears.

Author information

1
Department of Medicine, School of Medicine, Washington University, Saint Louis, MO 63110, US. Electronic address: miner@wustl.edu.
2
Department of Ophthalmology and Visual Sciences, School of Medicine, Washington University, Saint Louis, MO 63110, US.
3
Department of Medicine, School of Medicine, Washington University, Saint Louis, MO 63110, US.
4
Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
5
Department of Psychiatry, School of Medicine, Washington University, Saint Louis, MO 63110, USA.
6
Department of Medicine, School of Medicine, Washington University, Saint Louis, MO 63110, US; Department of Molecular Microbiology, School of Medicine, Washington University, Saint Louis, MO 63110, USA; Department of Pathology and Immunology, School of Medicine, Washington University, Saint Louis, MO 63110, USA; The Center for Human Immunology and Immunotherapy Programs, School of Medicine, Washington University, Saint Louis, MO 63110, USA. Electronic address: diamond@borcim.wustl.edu.
7
Department of Medicine, School of Medicine, Washington University, Saint Louis, MO 63110, US; Department of Ophthalmology and Visual Sciences, School of Medicine, Washington University, Saint Louis, MO 63110, US; Department of Developmental Biology, School of Medicine, Washington University, Saint Louis, MO 63110, USA. Electronic address: apte@vision.wustl.edu.

Abstract

Zika virus (ZIKV) is an emerging flavivirus that causes congenital abnormalities and Guillain-Barré syndrome. ZIKV infection also results in severe eye disease characterized by optic neuritis, chorioretinal atrophy, and blindness in newborns and conjunctivitis and uveitis in adults. We evaluated ZIKV infection of the eye by using recently developed mouse models of pathogenesis. ZIKV-inoculated mice developed conjunctivitis, panuveitis, and infection of the cornea, iris, optic nerve, and ganglion and bipolar cells in the retina. This phenotype was independent of the entry receptors Axl or Mertk, given that Axl(-/-), Mertk(-/-), and Axl(-/-)Mertk(-/-) double knockout mice sustained levels of infection similar to those of control animals. We also detected abundant viral RNA in tears, suggesting that virus might be secreted from lacrimal glands or shed from the cornea. This model provides a foundation for studying ZIKV-induced ocular disease, defining mechanisms of viral persistence, and developing therapeutic approaches for viral infections of the eye.

PMID:
27612415
PMCID:
PMC5040391
DOI:
10.1016/j.celrep.2016.08.079
[Indexed for MEDLINE]
Free PMC Article

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