Herpes Simplex Keratitis and Related Syndromes

Choudhary, Anshoo; Higgins, Gareth; Kaye, Stephen B.

doi:10.1007/978-3-540-33681-5_7

Cited by 5 publications

(9 citation statements)

References 183 publications

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“…1 In the eye, LL-37 is expressed by the cornea epithelium and has been reported to have potent antiviral activity against herpes simplex virus (HSV)-1, 2 the main infectious cause of vision loss and blindness worldwide. 3 The global incidence of ocular infection by HSV-1 is roughly 1.5 million per year, including 40,000 new cases of severe monocular visual impairment or blindness each year. 4 Once infected with HSV-1, the corneal nerves become sites of latency for the viruses and there is evidence for corneal latency as well.…”

Section: Introductionmentioning

confidence: 99%

“…5 Recurrent disease that can lead to uncontrolled stromal inflammation, scarring, and hence, corneal opacity and vision loss, is referred to as herpes simplex keratitis (HSK). 3 The only widespread treatment available for a scarred cornea is transplantation. However, this is a high-risk procedure with a low success rate of retaining a clear corneal graft, as the surgery itself has been reported to cause viral reactivation and an inflammation cascade that will affect the new graft.…”

Section: Introductionmentioning

confidence: 99%

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Cathelicidin LL-37 and HSV-1 Corneal Infection: Peptide Versus Gene Therapy

Lee

Buznyk

Kuffová

et al. 2014

Trans. Vis. Sci. Tech.

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Purpose: To evaluate the potential utility of collagen-based corneal implants with anti-Herpes Simplex Virus (HSV)-1 activity achieved through sustained release of LL-37, from incorporated nanoparticles, as compared with cell-based delivery from model human corneal epithelial cells (HCECs) transfected to produce endogenous LL-37. Methods:We tested the ability of collagen-phosphorylcholine implants to tolerate the adverse microenvironment of herpetic murine corneas. Then, we investigated the efficacy of LL-37 peptides delivered through nanoparticles incorporated within the corneal implants to block HSV-1 viral activity. In addition, LL-37 complementary DNA (cDNA) was transferred into HCECs to confer viral resistance, and their response to HSV-1 infection was examined.Results: Our implants remained in herpetic murine corneas 7 days longer than allografts. LL-37 released from the implants blocked HSV-1 infection of HCECs by interfering with viral binding. However, in pre-infected HCECs, LL-37 delayed but could not prevent viral spreading nor clear viruses from the infected cells. HCECs transfected with the LL-37 expressed and secreted the peptide. Secreted LL-37 inhibited viral binding in vitro but was insufficient to protect cells completely from HSV-1 infection. Nevertheless, secreted LL-37 reduced both the incidence of plaque formation and plaque size.Conclusion: LL-37 released from composite nanoparticle-hydrogel corneal implants and HCEC-produced peptide, both showed anti-HSV-1 activity by blocking binding. However, while both slowed down virus spread, neither was able on its own to completely inhibit the viruses.Translational Relevance: LL-37 releasing hydrogels may have potential utility as corneal substitutes for grafting in HSV-1 infected corneas, possibly in combination with LL-37 producing therapeutic cells.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cathelicidin LL-37 and HSV-1 Corneal Infection: Peptide Versus Gene Therapy

Lee

Buznyk

Kuffová

et al. 2014

Trans. Vis. Sci. Tech.

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“…They cause cold sores, herpetic keratitis and genital herpes [3][4][5]. An estimated 400 million people worldwide are currently infected by HSV-2 and infection of HSV-1 is spreading to developed regions like USA, Western Europe, Australia and New Zealand [WHO Fact Sheet, 2015].…”

Section: Introductionmentioning

confidence: 99%

Denovo Designing, Virtual Screening and Lead Optimization of Potential Drug Candidate for Herpes Disease

Sharma¹,

Rawat²,

Mehta³

2015

J Microb Biochem Technol

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“…During the course of herpetic keratitis, the HSV-induced cytopathogenicity together with the chronic immune-inflammatory reaction can trigger stromal scarring, thinning and neovascularization, leading to permanent vision impairment. Herpetic keratitis therefore remains a frequent infectious cause of blindness in many countries (Biswas and Rouse 2005;Choudhary et al 2008;Rowe et al 2013).…”

Section: Introductionmentioning

confidence: 99%

“…Systemic and local stressors can interrupt the latency and induce viral reactivation, leading to recrudescent infections. The cytopathogenic mechanism of diseases caused by HSV-1 and HSV-2 involves indirect, immune processes and direct, virus-mediated events (Biswas and Rouse 2005;Holdeman 2005; Kaye and Choudhary 2006;Fatahzadeh and Schwartz 2007;Choudhary et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Herpes simplex virus types 1 and 2 modulate autophagy in SIRC corneal cells

et al. 2014

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Autophagy and apoptosis function as important early cellular defense mechanisms in infections and other diseases. The outcome of an infection is determined by a complex interplay between the pathogenic microorganism and these intracellular pathways. To better understand the cytopathogenicity of Herpes simplex virus types 1 and 2 (HSV-1 and -2), we studied the effect of these viruses on the autophagic and apoptotic processes in the SIRC corneal cell line. Infection with the KOS strain of HSV-1 and a wild-type strain of HSV-2 enhanced autophagosome formation, triggered cytoplasmic acidification, increased LC3B lipidation and elevated the ratio of apoptotic cells. The autophagy inhibitor bafilomycin A1 triggered a significant increase in the apoptotic responses of HSV-1-and HSV-2-infected cells. Thus, both HSV types affect autophagy and apoptosis in a coordinated fashion, and autophagy plays cytoprotective role in HSV-infected cells via antagonizing apoptosis. Together these data implicate autophagy in the pathogenic mechanism of herpetic keratitis.[Petrovski G, Pásztor K, Orosz L, Albert R, Mencel E, Moe MC, Kaarniranta K, Facskó A and Megyeri K 2014 Herpes simplex virus types 1 and 2 modulate autophagy in SIRC corneal cells.

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Herpes Simplex Keratitis and Related Syndromes

Cited by 5 publications

References 183 publications

Cathelicidin LL-37 and HSV-1 Corneal Infection: Peptide Versus Gene Therapy

Cathelicidin LL-37 and HSV-1 Corneal Infection: Peptide Versus Gene Therapy

Denovo Designing, Virtual Screening and Lead Optimization of Potential Drug Candidate for Herpes Disease

Herpes simplex virus types 1 and 2 modulate autophagy in SIRC corneal cells

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