Journal
CELL REPORTS
Volume 16, Issue 12, Pages 3208-3218Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2016.08.079
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Funding
- NIH [R01 AI073755, R01 AI101400, R01 AI104972, R01 EY019287, P30 EY02687, R01 AI067380]
- Research to Prevent Blindness
- Schulak Family Gift Fund for Retinal Research
- Jeffrey Fort Innovation Fund
- Rheumatology Research Foundation Scientist Development Award
- Intellectual and Developmental Disabilities Research Center at Washington University [NIH/NICHD U54 HD087011]
- Moderna
- Sanofi
- Visterra
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Zika virus (ZIKV) is an emerging flavivirus that causes congenital abnormalities and Guillain-Barre 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 ZIK-Vinduced ocular disease, defining mechanisms of viral persistence, and developing therapeutic approaches for viral infections of the eye.
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