Emergence of cross-resistant herpes simplex virus following topical drug therapy in rabbit keratitis

Fardeau, Christine; Langlois, M.; Mathys, Blake A.; Rafales, P.; Nugier, F.; Godard, Virginie; Aymard, M.; Denis, Jean‐Noël

doi:10.3109/02713689109020372

Cited by 12 publications

(6 citation statements)

References 11 publications

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“…9,10 Although significant clinical resistance to TFT has yet to be observed, resistant strains can be isolated in culture. 11 Corticosteroids, which suppress the immune system, should be used only in conjunction with an antiviral and can create problems such as steroid-induced glaucoma. 12 These limitations reveal a need for the development of new therapies with reduced toxicity and alternative mechanisms of action.…”

Section: Results Tat-cdmentioning

confidence: 99%

A Cationic Peptide, TAT-Cd⁰, Inhibits Herpes Simplex Virus Type 1 Ocular Infection In Vivo

Jose¹,

Larsen

Gauger

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To test the in vivo activity of a peptide derived from the protein transducing domain of the human immunodeficiency virus (HIV) Tat protein, TAT-Cd 0 , in a murine herpes simplex type 1 (HSV-1) keratitis model. METHODS.The efficacy of TAT-Cd 0 was assessed in a postinfection treatment model with different concentrations (1 mg/mL, 0.1 mg/mL, 0.01 mg/mL) of the peptide in one of four delivery vehicles: artificial tears, PBS, methylcellulose, and aquaphor cream. Treatment began within 4 or 24 hours postinfection. Viral titers in the tear film were determined by plaque assay. RESULTS. TAT-Cd0 reduced the severity of keratitis in all of the delivery vehicles tested when treatment started, 4 hours postinfection. Peptide in the tears or PBS delivery vehicle had the most significant reduction in disease severity and delayed the onset of vascularization and stromal keratitis. The percentage of mice presenting with disease was also significantly reduced and viral titers were reduced by 1 log at 24 hours postinfection in mice treated with 1 mg/mL TAT-Cd 0 , suggesting that inhibiting replication early is sufficient to achieve clinical effects. Lower concentrations were not effective and delaying treatment by 24 hours was also not effective.CONCLUSIONS. This study shows that TAT-Cd 0 is an effective antiviral against HSV-1 strain KOS when applied shortly postinfection and that aqueous-based formulations are more suitable. (Invest Ophthalmol Vis Sci.

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Section: Results Tat-cdmentioning

confidence: 99%

A Cationic Peptide, TAT-Cd⁰, Inhibits Herpes Simplex Virus Type 1 Ocular Infection In Vivo

Jose¹,

Larsen

Gauger

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…while no significant difference was observed with the 0.05% ganciclovir treated eyes. In the placebo group, corneal clouding was observed initially on day 7 postinoculation (Table 1) and corneal vascularization on day 10 (Table 2), with both phenomena increasing until day 14 (last observation day). All 8 eyes exhibited clouding and 7 showed vascularization.…”

Section: Clinical Efficacy Of Treatmentsmentioning

confidence: 96%

“…This strain was selected because of its sensitivity to ganciclovir, acyclovir, and as well as to idoxuridine, idoxycytidine, trifluridine, vidarabine and bromovinyldesoxyuridine, in vivo in experimental rabbit keratitis and in vitro by dye-uptake assay (10). By successive assays performed on Vero cells, the mean effective dose 50% (ED 50) values and the corresponding standard deviations (SD) were 260 ± 60 ng/mL for ganciclovir and 180 ± 63 ng/mL for acyclovir.…”

Section: Virus Strainmentioning

confidence: 99%

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Ganciclovir Ophthalmic Gel in Herpes Simplex Virus Rabbit Keratitis: Intraocular Penetration and Efficacy

Castela¹,

Vermerie²,

Chast³

et al. 1994

Journal of Ocular Pharmacology and Therapeutics

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A chronic administration of three ganciclovir gels (0.2%, 0.05%, 0.0125%) was compared with a placebo gel and a 3% acyclovir ophthalmic ointment in the treatment of HSV-1 rabbit keratitis. All the ganciclovir gels showed a clinical efficacy: a significant reduction of the corneal ulcer area, clouding and vascularization (p < 0.05) and a fast inhibition of HSV isolates into tear film with the 0.2% and 0.05% ganciclovir gels. However the efficacy was slower than using acyclovir ointment. No significant difference could be shown between the 0.2% and 0.05% ganciclovir gels or the 0.05% ganciclovir gel and the acyclovir treatment on viral isolation, when it was performed on pooled samples.The distribution of ganciclovir and acyclovir into the rabbit eyes (HPLC methods), were similar but markedly higher in solid tissues than ocular fluids. It might explain the recovery from tissue damages. The mean corneal ganciclovir concentrations were largely higher than ED 50 of ganciclovir for HSV-1. No toxicity was expected, due to very limited systemic availability.This study suggests a comparable activity on HSV-1 superficial keratitis between 0.05%, 0.2% ganciclovir gels and 3% acyclovir ointment. Higher concentration of ganciclovir gels are probably necessary in order to treat the HSV-1 kerato-uveitis.

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“…The virus preparation was stored at -80 ° C. This strain is sensitive to idoxuridine (IDU), adenine-arabinoside (ARA-A), trifluorothymidine (TFT) and acyclovir (ACV), in vitro and in vivo (rabbit herpes keratitis [10,12]). …”

Section: Virus Preparationmentioning

confidence: 99%

Fibroblast growth factor 2, heparin and suramin reduce epithelial ulcer development in experimental HSV-1 keratitis

Rieck

Denis

Peters

et al. 1997

Graefe's Arch Clin Exp Ophthalmol

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Emergence of cross-resistant herpes simplex virus following topical drug therapy in rabbit keratitis

Cited by 12 publications

References 11 publications

A Cationic Peptide, TAT-Cd⁰, Inhibits Herpes Simplex Virus Type 1 Ocular Infection In Vivo

A Cationic Peptide, TAT-Cd⁰, Inhibits Herpes Simplex Virus Type 1 Ocular Infection In Vivo

Ganciclovir Ophthalmic Gel in Herpes Simplex Virus Rabbit Keratitis: Intraocular Penetration and Efficacy

Fibroblast growth factor 2, heparin and suramin reduce epithelial ulcer development in experimental HSV-1 keratitis

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Emergence of cross-resistant herpes simplex virus following topical drug therapy in rabbit keratitis

Cited by 12 publications

References 11 publications

A Cationic Peptide, TAT-Cd0, Inhibits Herpes Simplex Virus Type 1 Ocular Infection In Vivo

A Cationic Peptide, TAT-Cd0, Inhibits Herpes Simplex Virus Type 1 Ocular Infection In Vivo

Ganciclovir Ophthalmic Gel in Herpes Simplex Virus Rabbit Keratitis: Intraocular Penetration and Efficacy

Fibroblast growth factor 2, heparin and suramin reduce epithelial ulcer development in experimental HSV-1 keratitis

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Product

Resources

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A Cationic Peptide, TAT-Cd⁰, Inhibits Herpes Simplex Virus Type 1 Ocular Infection In Vivo

A Cationic Peptide, TAT-Cd⁰, Inhibits Herpes Simplex Virus Type 1 Ocular Infection In Vivo