Interferon-stimulated gene 15 (ISG15) restricts Zika virus replication in primary human corneal epithelial cells

Area of Science:

• Ophthalmology
• Virology
• Immunology

Background:

• Zika virus (ZIKV) is a known human pathogen associated with ocular complications.
• ZIKV has been detected in human and animal tears, indicating potential ocular shedding.
• The infectivity and immune response within corneal cells remain incompletely understood.

Purpose of the Study:

• To investigate the susceptibility of corneal epithelial cells to ZIKV infection.
• To analyze the innate inflammatory and antiviral immune responses in corneal cells upon ZIKV exposure.
• To elucidate the role of Interferon-Stimulated Gene 15 (ISG15) in the corneal antiviral defense against ZIKV.

Main Methods:

• Primary human corneal epithelial cells (Pr. HCECs) and an immortalized cell line (HUCL) were infected with ZIKV and dengue virus (DENV).
• Viral infectivity was assessed using immunostaining and plaque assays.
• Gene and protein expression analyses (qRT-PCR, immunoblot) were performed, alongside ISG15 manipulation (silencing and supplementation).

Main Results:

• Pr. HCECs, but not HUCL cells, were permissive to ZIKV and DENV3.
• ZIKV infection induced expression of viral recognition receptors, inflammatory genes (CXCL10, CCL5), and antiviral genes (IFNs, MX1, OAS2, ISG15) in Pr. HCECs.
• ISG15 silencing enhanced ZIKV infectivity, while ISG15 supplementation reduced it by inactivating the virus and inhibiting entry; ZIKV infection led to Pr. HCECs cell death.

Conclusions:

• Zika virus (ZIKV) readily infects and replicates in primary human corneal epithelial cells.
• The cornea may serve as a persistent reservoir for ZIKV.
• ZIKV infection of corneal cells presents a potential risk for transmission via corneal transplantation.