HSV-1 and Zika Virus but Not SARS-CoV-2 Replicate in the Human Cornea and Are Restricted by Corneal Type III Interferon
Jonathan J. Miner,
Derek J. Platt,
Cyrus M. Ghaznavi,
Pallavi Chandra,
Andrea Santeford,
Amber M. Menos,
Zhenyu Dong,
Erin R. Wang,
Wei Qian,
Elysse S. Karozichian,
Jennifer A. Philips,
Rajendra S. Apte
Affiliations
Jonathan J. Miner
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Corresponding author
Derek J. Platt
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA
Cyrus M. Ghaznavi
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Pallavi Chandra
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Andrea Santeford
Department of Ophthalmology, Washington University School of Medicine, St. Louis, MO 63110, USA
Amber M. Menos
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Zhenyu Dong
Department of Ophthalmology, Washington University School of Medicine, St. Louis, MO 63110, USA
Erin R. Wang
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Wei Qian
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Elysse S. Karozichian
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Jennifer A. Philips
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA
Rajendra S. Apte
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Ophthalmology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; Corresponding author
Summary: 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.
