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Common and new acyclovir resistant herpes simplex virus-1 mutants causing bilateral recurrent herpetic keratitis in an immunocompetent patient.
- Source :
-
The Journal of infectious diseases [J Infect Dis] 2014 Feb 01; Vol. 209 (3), pp. 345-9. Date of Electronic Publication: 2013 Aug 14. - Publication Year :
- 2014
-
Abstract
- We investigated thymidine kinase (tk) mutants isolated during multiple episodes of recurrent bilateral acyclovir resistant herpes simplex keratitis in an immunocompetent patient. From one eye, we found a single guanine insertion, previously shown to greatly reduce TK expression, and from the other, a previously unidentified substitution, which genetic experiments confirmed confers drug resistance. The substitution, although distant from substrate binding sites, reduced thymidine phosphorylation 10-20-fold, and acyclovir phosphorylation >100-fold. This phenotype should permit reactivation from latency to cause recurrent disease. The results may have implications for the prevalence and prevention of acyclovir resistance in patients with herpes simplex keratitis.
- Subjects :
- Adult
Amino Acid Substitution
DNA, Viral chemistry
DNA, Viral genetics
Herpesvirus 1, Human isolation & purification
Humans
Male
Molecular Sequence Data
Mutant Proteins genetics
Mutant Proteins metabolism
Mutation, Missense
Phosphorylation
Point Mutation
Recurrence
Sequence Analysis, DNA
Thymidine metabolism
Thymidine Kinase genetics
Thymidine Kinase metabolism
Viral Proteins genetics
Viral Proteins metabolism
Acyclovir pharmacology
Antiviral Agents pharmacology
Drug Resistance, Viral
Herpesvirus 1, Human drug effects
Keratitis, Herpetic virology
Subjects
Details
- Language :
- English
- ISSN :
- 1537-6613
- Volume :
- 209
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Journal of infectious diseases
- Publication Type :
- Academic Journal
- Accession number :
- 23945375
- Full Text :
- https://doi.org/10.1093/infdis/jit437