Resistance testing of clinical herpes simplex virus type 2 isolates collected over 4 decades

International Journal of Medical Microbiology : IJMM
Kathrin Bohn-WippertAndreas Sauerbrei

Abstract

There is only little information about the role of mutations of the thymidine kinase (TK) and DNA polymerase (pol) genes of herpes simplex virus type 2 (HSV-2) for the development of antiviral resistance. In this study, the polymorphism of TK and DNA pol genes was examined in 82 clinical isolates collected routinely between 1973 and 2013. If novel, presently unclear or resistance-related mutations were found, the resistance phenotype against acyclovir (ACV) and foscarnet (FOS) was analyzed. The four novel amino acid changes G150D, A157T, R248W, L342W and the hitherto phenotypically unclear substitution T131M within the TK gene were identified as natural polymorphisms. Within the DNA pol gene, 17 novel substitutions and the to-date unclear change R628C were characterized as part of natural gene polymorphism. Two novel DNA pol mutations were linked to resistance (M910T) and weak susceptibility to ACV (684 insertion ED), respectively. In one isolate, the genomic cause of ACV resistance could not be identified. Phylogenetic analysis including sequences of this study and of the GenBank revealed a hierarchy of mutation clusters in TK displaying G39E as first common mutation step, followed by N78D and L140F. In conclusion, the present...Continue Reading

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Citations

Sep 14, 2015·International Journal of Medical Microbiology : IJMM·Ulrich VogelMary Slack
May 14, 2016·PloS One·Johanna G MitterreiterWerner J D Ouwendijk
Jan 21, 2016·Antimicrobial Agents and Chemotherapy·Peter J IrelandLynda A Morrison

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