Varicella Zoster Virus Induces Differential Cell-Type Specific Responses in Human Corneal Epithelial Cells and Keratocytes

Investigative Ophthalmology & Visual Science
Christina N ComoMaria A Nagel

Abstract

While VZV DNA and antigen have been detected in acute and chronic VZV keratitis, it is unclear whether productive infection of corneal cells is ongoing or whether residual, noninfectious VZV antigens elicit inflammation. Herein, we examined VZV-infected primary human corneal epithelial cells (HCECs) and keratocytes (HKs) to elucidate the pathogenesis of VZV keratitis. HCECs and HKs were mock- or VZV infected. Seven days later, cells were examined for morphology, proinflammatory cytokine and matrix metalloproteinase (MMP) release, ability to recruit peripheral blood mononuclear cells (PBMCs) and neutrophils, and MMP substrate cleavage. Both cell types synthesized infectious virus. VZV-infected HCECs proliferated, whereas VZV-infected HKs died. Compared to mock-infected cells, VZV-infected HCECs secreted significantly more IL-6, IL-8, IL-10, and IL-12p70 that were confirmed at the transcript level, and MMP-1 and MMP-9; conditioned supernatant attracted PBMCs and neutrophils and cleaved MMP substrates. In contrast, VZV-infected HKs suppressed cytokine secretion except for IL-8, which attracted neutrophils, and suppressed MMP release and substrate cleavage. Overall, VZV-infected HCECs recapitulate findings of VZV keratitis with res...Continue Reading

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Citations

Mar 6, 2019·The Journal of Infectious Diseases·Anna M BlackmonMaria A Nagel

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Datasets Mentioned

BETA
MH379685

Methods Mentioned

BETA
antibody assay
confocal microscopy
Assay

Software Mentioned

Meso Scale Discovery
Fiji
ImageJ
GraphPad Prism

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