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.
Highlights
Likewise, it remains unclear whether infection of HCE cells by Herpes simplex virus (HSV)-1 reflects the uniqueness seen with the corneal infection
Using a recombinant HSV-1 (KOS) gL86 virus that encodes a β-galactosidase gene[19] at MOIs 1, 0.1 and 0.01, we observed that viral entry at MOI 1 was the highest and the least amount of viral entry was observed with MOI 0.01 in HCE cells (Fig. 1a)
To further confirm that viral entry is MOI-dependent, HCE cells were infected with HSV-1 (KOS) at MOIs 1, 0.1 and 0.01 for 6 hrs and immunoblotted for infected cell protein (ICP0), an early viral gene product that is transcribed upon entry
Summary
Likewise, it remains unclear whether infection of HCE cells by HSV-1 reflects the uniqueness seen with the corneal infection. It is unclear whether the cytokine response has any connection with the MOI of viral intruders. The latter could be crucial for controlling the disease and for signaling the influx of immune cells[16]. It is unclear whether the highly restricted spread of the infection in the cornea is due to the involvement of the immune system or the cornea itself having an inherent ability to restrict the infection. We demonstrate that cultured corneas are capable of restricting the infection and can provide an excellent model for studying the uniqueness of virus spread in the eye and testing the effects of antiviral drugs
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