Commercial human 3D corneal epithelial equivalents for modeling epithelial infection in herpes keratitis

Herpes stromal keratitis is the leading cause of infectious blindness in the western world. Infection by HSV1 is most common, but VZV and hCMV also infect the cornea. Multiple models of HSV1 corneal infection exist, but none for VZV and hCMV because of their host specificity. Here, we used commercially available 3D human corneal epithelial equivalents (HCEE) to study infection by these herpesviruses. HCEE was infected by HSV-1 and hCMV without requiring scarification and resulted in spreading infections. Spread of HSV-1 infection was rapid, while that of hCMV was slow. In contrast, infections with VZV required damage to the HCEE and did not spread. Acyclovir dramatically reduced replication of HSV-1 in this model. We conclude that highly quality-controlled, readily available HCEE is a useful model to study human-restricted herpesvirus infection of the human corneal epithelium and for screening of antiviral drugs for treating HSK in an 3D model system. •Episkin Epicorneal is a 3D human corneal epithelial model validated for irritation testing.•The 3D corneal model can be cultured at the air-liquid interface for up to 21 days retaining 3D stratification.•HSV1 and hCMV infect the 3D corneal model and infections spread with time.•VZV infects this 3D model but does not spread.•Rapid and simple testing of anti-viral drugs is possible using fluorescent herpesviruses.