HSV-1 and Zika Virus but Not SARS-CoV-2 Replicate in the Human Cornea and Are Restricted by Corneal Type III Interferon

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. [Display omitted] •The type III interferon receptor (IFNλR1) inhibits viral growth in the human cornea•Zika virus is transmissible by corneal transplantation in mice•IFN-λ limits herpes simplex virus 1 and Zika virus growth in the human cornea•SARS-CoV-2 does not replicate in human corneal tissue Miner et al. report that type III interferon (IFN-λ) and its receptor (IFNλR1) restrict herpes simplex virus 1 (HSV-1) and Zika virus (ZIKV) growth in the human cornea. Human corneal explants did not support severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, even after blockade of the type III IFN receptor.