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

被引:210
作者
Miner, Jonathan J. [1 ]
Sene, Abdoulaye [2 ]
Richner, Justin M. [1 ]
Smith, Amber M. [1 ]
Santeford, Andrea [2 ]
Ban, Norimitsu [2 ]
Weger-Lucarelli, James [3 ]
Manzella, Francesca [4 ]
Rueuckert, Claudia [3 ]
Govero, Jennifer [1 ]
Noguchi, Kevin K. [4 ]
Ebel, Gregory D. [3 ]
Diamond, Michael S. [1 ,5 ,6 ,7 ]
Apte, Rajendra S. [1 ,2 ,8 ]
机构
[1] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA
[3] Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA
[4] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA
[5] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA
[6] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
[7] Washington Univ, Sch Med, Ctr Human Immunol & Immunotherapy Programs, St Louis, MO 63110 USA
[8] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA
关键词
HEPATITIS-C VIRUS; EBOLA-VIRUS; TRANSMISSION; ALPHA/BETA; RESPONSES; CELLS; MODEL;
D O I
10.1016/j.celrep.2016.08.079
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:3208 / 3218
页数:11
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