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George Azar, Sonia Burrel, Serge Doan, Isabelle Cochereau, Henri Agut, David Boutolleau, Eric Gabison; Acyclovir-Resistant Corneal HSV-1 Isolates From Two Immunocompetent Patients With Recurrent Herpetic Keratitis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5858.
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© ARVO (1962-2015); The Authors (2016-present)
To report two unpreviously described mutations potentially associated with Acyclovir-resistant corneal HSV-1 isolates in two immunocompetent patients.
We present two cases of patients aged 77 and 76 years old with a past history of recurrent HK, who developed HK. Despite a well-conducted antiviral treatment with Valacyclovir (VACV) per os (1g t.i.d), new dendritic lesions appeared raising the suspicion of Acyclovir (ACV) resistance. Corneal epithelial scrapping was performed for cell culture and susceptibility testing of HSV-1 isolates to ACV and Foscarnet (FOS). Full-length Thymidine Kinase (UL23) and DNA polymerase (UL30) genes were also amplified and sequenced for genotypic antiviral resistance testing.
HSV-1 isolates from epithelial corneal cells were obtained in Vero cell culture for both patients. The susceptibility to ACV and FOS was determined by both phenotypic and genotypic methods. Using a plaque-reduction assay, both HSV-1 isolates were evidenced to be resistant to ACV (IC50=35 µM) and sensitive to FOS (IC50<66 µM). The genotypic antiviral resistance testing for the UL23 and UL30 genes revealed four well-known natural polymorphisms. An unpreviously described amino acid change Y53D potentially associated with ACV resistance was detected on the Thymidine Kinase gene in the first patient. Another new mutation S775N associated with ACV resistance was detected on the DNA Polymerase gene in the second patient as well.
These two cases underline the possible emergence of corneal ACV-resistant HSV-1 among immunocompetent patients with recurrent HK. Moreover, the implication of the newly identified changes Y53D and S775N in the acquisition of ACV-resistance is going to be investigated using Thymidine Kinase and DNA Polymerase gene site-directed mutagenesis method.
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