Sauerbrei Andreas, Bohn-Wippert Kathrin, Kaspar Marisa, Krumbholz Andi, Karrasch Matthias, Zell Roland
Institute of Virology and Antiviral Therapy, German Consulting Laboratory for HSV and VZV, Jena University Hospital, Jena, Germany
Institute of Virology and Antiviral Therapy, German Consulting Laboratory for HSV and VZV, Jena University Hospital, Jena, Germany.
J Antimicrob Chemother. 2016 Jan;71(1):6-16. doi: 10.1093/jac/dkv285. Epub 2015 Oct 3.
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.
1型和2型单纯疱疹病毒(HSV-1和HSV-2)基因型耐药性检测的应用正在增加,因为检测结果的快速可得性显著改善了严重感染的治疗,尤其是在免疫功能低下的患者中。然而,一个基本前提是要广泛了解胸苷激酶(TK)和DNA聚合酶(pol)基因中的自然多态性和耐药相关突变,临床使用的高效抗病毒药物靶向的是DNA聚合酶(Pol)酶。因此,本综述展示了一个关于HSV-1和HSV-2的TK和DNA pol基因所有非同义突变的数据库,这些突变与耐药性或自然基因多态性的关联已通过表型和/或功能试验得以阐明。此外,还总结了用于验证自然多态性或耐药突变的实验室方法。该数据库可极大地有助于临床HSV-1和HSV-2菌株基因型耐药性检测结果的解读。