title: Cultured corneas show dendritic spread and restrict herpes simplex virus infection that is not observed with cultured corneal cells.
abstract: Herpes simplex virus-1 (HSV-1) causes life-long morbidities in humans. While fever blisters are more common, occasionally the cornea is infected resulting in vision loss. A very intriguing aspect of HSV-1 corneal infection is that the virus spread is normally restricted to only a small fraction of cells on the corneal surface that connect with each other in a dendritic fashion. Here, to develop a comprehensive understanding of the susceptibility of human corneal epithelial (HCE) cells to HSV-1 infection, we infected HCE cells at three different dosages of HSV-1 and measured the outcomes in terms of viral entry, gene and protein expression, viral replication and cytokine induction. In cultured cells, infectivity and cytokine induction were observed even at the minimum viral dosage tested, while a more pronounced dose-restricted infectivity was seen in ex vivo cultures of porcine corneas. Use of fluorescent HSV-1 virions demonstrated a pattern of viral spread ex vivo that mimics clinical findings. We conclude that HCE cell cultures are highly susceptible to infection whereas the cultured corneas demonstrate a higher ability to restrict the infection even in the absence of systemic immune system. The restriction is helped in part by local interferon response and the unique cellular architecture of the cornea.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, IL 60612, USA.
authors.forename: Neel
authors.initials: N
authors.lastname: Thakkar
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, IL 60612, USA.|Department of Bioengineering, University of Illinois at Chicago, IL 60612, USA.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Jaishankar
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, IL 60612, USA.|Department of Microbiology and Immunology, University of Illinois at Chicago, IL 60612, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Agelidis
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, IL 60612, USA.
authors.forename: Tejabhiram
authors.initials: T
authors.lastname: Yadavalli
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, IL 60612, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Mangano
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, IL 60612, USA.
authors.forename: Shrey
authors.initials: S
authors.lastname: Patel
authors.affiliation: Department of Microbiology, Canakkale Onsekiz Mart University, Canakkale 17020, Turkey.
authors.forename: Sati Zeynep
authors.initials: SZ
authors.lastname: Tekin
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, IL 60612, USA.|Department of Bioengineering, University of Illinois at Chicago, IL 60612, USA.|Department of Microbiology and Immunology, University of Illinois at Chicago, IL 60612, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Shukla
mesh_terms: D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D003315:Cornea / Q000502:physiology* / Q000821:virology*; D016207:Cytokines / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D006561:Herpes Simplex / Q000821:virology*; D006801:Humans; D009924:Organ Culture Techniques; D018139:Simplexvirus / Q000502:physiology*; D053586:Virus Internalization; D057074:Virus Release; D014779:Virus Replication
chemical_list: D016207:Cytokines