Zika Virus Infection in Mice Causes Panuveitis with Shedding of Virus in Tears.
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.
Department of Medicine, School of Medicine, Washington University, Saint Louis, MO 63110, US. Electronic address: miner@wustl.edu.
Jonathan J
JJ
Miner
Department of Ophthalmology and Visual Sciences, School of Medicine, Washington University, Saint Louis, MO 63110, US.
Abdoulaye
A
Sene
Department of Medicine, School of Medicine, Washington University, Saint Louis, MO 63110, US.
Justin M
JM
Richner
Department of Medicine, School of Medicine, Washington University, Saint Louis, MO 63110, US.
Amber M
AM
Smith
Department of Ophthalmology and Visual Sciences, School of Medicine, Washington University, Saint Louis, MO 63110, US.
Andrea
A
Santeford
Department of Ophthalmology and Visual Sciences, School of Medicine, Washington University, Saint Louis, MO 63110, US.
Norimitsu
N
Ban
Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
James
J
Weger-Lucarelli
Department of Psychiatry, School of Medicine, Washington University, Saint Louis, MO 63110, USA.
Francesca
F
Manzella
Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Claudia
C
Rückert
Department of Medicine, School of Medicine, Washington University, Saint Louis, MO 63110, US.
Jennifer
J
Govero
Department of Psychiatry, School of Medicine, Washington University, Saint Louis, MO 63110, USA.
Kevin K
KK
Noguchi
Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Gregory D
GD
Ebel
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.
Michael S
MS
Diamond
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.
Rajendra S
RS
Apte
D000818:Animals; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015864:Panuveitis / Q000821:virology*; D011518:Proto-Oncogene Proteins / Q000172:deficiency; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency; D013666:Tears / Q000821:virology*; D017201:Virus Shedding / Q000502:physiology*; D000071243:Zika Virus Infection / Q000821:virology*; D000076202:c-Mer Tyrosine Kinase / Q000172:deficiency; D000094963:Axl Receptor Tyrosine Kinase
D011518:Proto-Oncogene Proteins; C490767:Mertk protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase; D000094963:Axl Receptor Tyrosine Kinase; C000722290:AXL receptor tyrosine kinase, mouse