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

Jonathan J. Miner, Abdoulaye Sene, Justin M. Richner, Amber M. Smith, Andrea Santeford, Norimitsu Ban, James Weger-Lucarelli, Francesca Manzella, Claudia Rückert, Jennifer Govero, Kevin K. Noguchi, Gregory D. Ebel, Michael S. Diamond, Rajendra S. Apte

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155 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3208-3218
Number of pages11
JournalCell Reports
Volume16
Issue number12
DOIs
Publication statusPublished - 2016 Sep 20

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Miner, J. J., Sene, A., Richner, J. M., Smith, A. M., Santeford, A., Ban, N., Weger-Lucarelli, J., Manzella, F., Rückert, C., Govero, J., Noguchi, K. K., Ebel, G. D., Diamond, M. S., & Apte, R. S. (2016). Zika Virus Infection in Mice Causes Panuveitis with Shedding of Virus in Tears. Cell Reports, 16(12), 3208-3218. https://doi.org/10.1016/j.celrep.2016.08.079