@article{81fbd9aebca449ffa4448a2f1c1ac862,
title = "HSV-1 and Zika Virus but Not SARS-CoV-2 Replicate in the Human Cornea and Are Restricted by Corneal Type III Interferon",
abstract = "Here, we report our studies of immune-mediated regulation of Zika virus (ZIKV), herpes simplex virus 1 (HSV-1), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the human cornea. We find that ZIKV can be transmitted via corneal transplantation in mice. However, in human corneal explants, we report that ZIKV does not replicate efficiently and that SARS-CoV-2 does not replicate at all. Additionally, we demonstrate that type III interferon (IFN-λ) and its receptor (IFNλR1) are expressed in the corneal epithelium. Treatment of human corneal explants with IFN-λ, and treatment of mice with IFN-λ eye drops, upregulates antiviral interferon-stimulated genes. In human corneal explants, blockade of IFNλR1 enhances replication of ZIKV and HSV-1 but not SARS-CoV-2. In addition to an antiviral role for IFNλR1 in the cornea, our results suggest that the human cornea does not support SARS-CoV-2 infection despite expression of ACE2, a SARS-CoV-2 receptor, in the human corneal epithelium.",
keywords = "COVID-19, SARS-CoV-2, Zika virus, cornea, coronavirus, eye, herpes simplex virus, interferon lambda, type III interferon",
author = "Miner, {Jonathan J.} and Platt, {Derek J.} and Ghaznavi, {Cyrus M.} and Pallavi Chandra and Andrea Santeford and Menos, {Amber M.} and Zhenyu Dong and Wang, {Erin R.} and Wei Qian and Karozichian, {Elysse S.} and Philips, {Jennifer A.} and Apte, {Rajendra S.}",
note = "Funding Information: We acknowledge the Washington University Morphology and Imaging Core for assistance with tissue processing and staining. We thank Dr. Todd Margolis at Washington University for advice on studies of HSV-1, and Dr. Jerry Y. Niederkorn{\textquoteright}s laboratory at University of Texas Southwestern Medical Center in Dallas for their expert advice regarding mouse corneal transplantation. The graphical abstract was created at biorender.com . D.J.P. is supported by the Washington University Chancellors Graduate Fellowship Program and the Initiative to Maximize Student Development . The Miner laboratory is supported by grants from the NIH ( K08 AR070918 , R21 EY027870 , and R01 AI143982 ) and the Department of Defense ( W81XWH-17-1-0111 ). The Apte laboratory is supported by grants from the NIH ( R01 EY027870 and 5P30 002687 ) and the Starr Foundation. Additional support to the Miner and Apte laboratories is provided by MidAmerica Transplant . The Philips laboratory is supported by grants from the NIH ( R01 AI087682 , R01 AI130454 , and R21 AI155380 ). NIH / National Center for Advancing Translational Sciences (NCATS) grant UL1 TR002345 also supported this work. Other support to the Apte laboratory is provided by an unrestricted grant to the Department of Ophthalmology and Visual Sciences from Research to Prevent Blindness and the Jeffery Fort Innovation Fund . Funding Information: We acknowledge the Washington University Morphology and Imaging Core for assistance with tissue processing and staining. We thank Dr. Todd Margolis at Washington University for advice on studies of HSV-1, and Dr. Jerry Y. Niederkorn's laboratory at University of Texas Southwestern Medical Center in Dallas for their expert advice regarding mouse corneal transplantation. The graphical abstract was created at biorender.com. D.J.P. is supported by the Washington University Chancellors Graduate Fellowship Program and the Initiative to Maximize Student Development. The Miner laboratory is supported by grants from the NIH (K08 AR070918, R21 EY027870, and R01 AI143982) and the Department of Defense (W81XWH-17-1-0111). The Apte laboratory is supported by grants from the NIH (R01 EY027870 and 5P30 002687) and the Starr Foundation. Additional support to the Miner and Apte laboratories is provided by MidAmerica Transplant. The Philips laboratory is supported by grants from the NIH (R01 AI087682, R01 AI130454, and R21 AI155380). NIH/National Center for Advancing Translational Sciences (NCATS) grant UL1 TR002345 also supported this work. Other support to the Apte laboratory is provided by an unrestricted grant to the Department of Ophthalmology and Visual Sciences from Research to Prevent Blindness and the Jeffery Fort Innovation Fund. D.J.P. P.C. A.S. A.M.M. Z.D. W.Q. and E.S.K. performed experiments. J.J.M. D.J.P. A.S. A.M.M. Z.D. and E.S.K. analyzed data. C.M.G. and E.R.W. analyzed data and wrote portions of the initial manuscript and edited subsequent versions of the manuscript. J.J.M. D.J.P. and E.R.W. wrote the final complete version of the manuscript. J.J.M. J.A.P. and R.S.A. conceived the project, analyzed data, and edited the final version of the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = nov,
day = "3",
doi = "10.1016/j.celrep.2020.108339",
language = "English",
volume = "33",
journal = "Cell Reports",
issn = "2211-1247",
number = "5",
}