title: Database on natural polymorphisms and resistance-related non-synonymous mutations in thymidine kinase and DNA polymerase genes of herpes simplex virus types 1 and 2.
abstract: The use of genotypic resistance testing of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) is increasing because the rapid availability of results significantly improves the treatment of severe infections, especially in immunocompromised patients. However, an essential precondition is a broad knowledge of natural polymorphisms and resistance-associated mutations in the thymidine kinase (TK) and DNA polymerase (pol) genes, of which the DNA polymerase (Pol) enzyme is targeted by the highly effective antiviral drugs in clinical use. Thus, this review presents a database of all non-synonymous mutations of TK and DNA pol genes of HSV-1 and HSV-2 whose association with resistance or natural gene polymorphism has been clarified by phenotypic and/or functional assays. In addition, the laboratory methods for verifying natural polymorphisms or resistance mutations are summarized. This database can help considerably to facilitate the interpretation of genotypic resistance findings in clinical HSV-1 and HSV-2 strains.
authors.affiliation: Institute of Virology and Antiviral Therapy, German Consulting Laboratory for HSV and VZV, Jena University Hospital, Jena, Germany andreas.sauerbrei@med.uni-jena.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Sauerbrei
authors.affiliation: Institute of Virology and Antiviral Therapy, German Consulting Laboratory for HSV and VZV, Jena University Hospital, Jena, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Bohn-Wippert
authors.affiliation: Institute of Virology and Antiviral Therapy, German Consulting Laboratory for HSV and VZV, Jena University Hospital, Jena, Germany.
authors.forename: Marisa
authors.initials: M
authors.lastname: Kaspar
authors.affiliation: Institute for Infection Medicine, Christian-Albrecht University and University Medical Center Schleswig-Holstein, Kiel, Germany.
authors.forename: Andi
authors.initials: A
authors.lastname: Krumbholz
authors.affiliation: Institute of Medical Microbiology, Jena University Hospital, Jena, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Karrasch
authors.affiliation: Institute of Virology and Antiviral Therapy, German Consulting Laboratory for HSV and VZV, Jena University Hospital, Jena, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Zell
mesh_terms: D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D024882:Drug Resistance, Viral; D005838:Genotype; D006801:Humans; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D018139:Simplexvirus / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics*
chemical_list: D013937:Thymidine Kinase; D004259:DNA-Directed DNA Polymerase