scholarly journals Characterization of the DNA Polymerase and Thymidine Kinase Genesof Herpes Simplex Virus Isolates from AIDS Patients in whom Acyclovirand Foscarnet Therapy Sequentially Failed

1999 ◽  
Vol 180 (2) ◽  
pp. 487-490 ◽  
Author(s):  
Isabelle Schmit ◽  
Guy Boivin
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Thymidine Kinase ◽  
Dna Polymerase ◽  
Aids Patients ◽  
Simplex Virus ◽  
Virus Isolates

Gene polymorphism of thymidine kinase and DNA polymerase in clinical strains of herpes simplex virus

2011 ◽  
Vol 16 (7) ◽  
pp. 989-997 ◽  
Author(s):  
Kathrin Bohn ◽  
Roland Zell ◽  
Michael Schacke ◽  
Peter Wutzler ◽  
Andreas Sauerbrei
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Gene Polymorphism ◽  
Thymidine Kinase ◽  
Dna Polymerase ◽  
Clinical Strains ◽  
Simplex Virus

Characterization of an aphidicolin-resistant mutant of herpes simplex virus type 2 which induces an altered viral DNA polymerase

Virology ◽  
1984 ◽  
Vol 135 (1) ◽  
pp. 87-96 ◽  
Author(s):  
Yukihiro Nishiyama ◽  
Satoru Suzuki ◽  
Manabu Yamauchi ◽  
Koichiro Maeno ◽  
Shonen Yoshida
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Dna Polymerase ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Resistant Mutant ◽  
Viral Dna ◽  
Simplex Virus

scholarly journals Low-Level Expression and Reversion both Contribute to Reactivation of Herpes Simplex Virus Drug-Resistant Mutants with Mutations on Homopolymeric Sequences in Thymidine Kinase

2006 ◽  
Vol 80 (13) ◽  
pp. 6568-6574 ◽  
Author(s):  
Anthony Griffiths ◽  
Malen A. Link ◽  
Caroline L. Furness ◽  
Donald M. Coen
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Thymidine Kinase ◽  
Trigeminal Ganglia ◽  
Virus Reactivation ◽  
Latently Infected ◽  
Low Levels ◽  
Simplex Virus ◽  
Translational Mechanisms ◽  
Virus Isolates

ABSTRACT Many acyclovir-resistant herpes simplex virus isolates from patients contain insertions or deletions in homopolymeric sequences in the thymidine kinase (TK) gene (tk). Viruses that have one (G8) or two (G9) base insertions in a run of seven G's (G string) synthesize low levels of active TK (TK-low phenotype), evidently via ribosomal frameshifting. These levels of TK can suffice to permit reactivation from latently infected mouse ganglia, but in a majority of ganglia, especially with the G9 virus, reactivation of virus that has reverted to the TK-positive phenotype predominates. To help address the relative contributions of translational mechanisms and reversion in reactivation, we generated viruses with a base either inserted or deleted just downstream of the G string. Both of these viruses had a TK-low phenotype similar to that of the G8 and G9 viruses but with less reversion. Both of these viruses reactivated from latently infected trigeminal ganglia, albeit inefficiently, and most viruses that reactivated had a uniformly TK-low phenotype. We also generated viruses that have one insertion in a run of six C's or one deletion in a run of five C's. These viruses lack measurable TK activity. However, they reactivated from latently infected ganglia, albeit inefficiently, with the reactivating viruses having reverted to the wild-type TK phenotype. Therefore, for G-string mutants, levels of active TK as low as 0.25% generated by translational mechanisms can suffice for reactivation, but reversion can also contribute. For viruses that lack TK activity due to mutations on other homopolymeric sequences, reactivation can occur via reversion.

scholarly journals Sequence Analysis of Herpes Simplex Virus 1 Thymidine Kinase and DNA Polymerase Genes from over 300 Clinical Isolates from 1973 to 2014 Finds Novel Mutations That May Be Relevant for Development of Antiviral Resistance

2015 ◽  
Vol 59 (8) ◽  
pp. 4938-4945 ◽  
Author(s):  
Susanne Schmidt ◽  
Kathrin Bohn-Wippert ◽  
Peter Schlattmann ◽  
Roland Zell ◽  
Andreas Sauerbrei
Keyword(s):  
Herpes Simplex Virus ◽  
Amino Acid ◽  
Herpes Simplex ◽  
Thymidine Kinase ◽  
Dna Polymerase ◽  
Herpes Simplex Virus 1 ◽  
Immunosuppressed Patients ◽  
Resistant Strains ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACTA total of 302 clinical herpes simplex virus 1 (HSV-1) strains, collected over 4 decades from 1973 to 2014, were characterized retrospectively for drug resistance. All HSV-1 isolates were analyzed genotypically for nonsynonymous mutations in the thymidine kinase (TK) and DNA polymerase (Pol) genes. The resistance phenotype against acyclovir (ACV) and/or foscarnet (FOS) was examined in the case of novel, unclear, or resistance-related mutations. Twenty-six novel natural polymorphisms could be detected in the TK gene and 69 in the DNA Pol gene. Furthermore, three novel resistance-associated mutations (two in the TK gene and one in the DNA Pol gene) were analyzed, and eight known but hitherto unclear amino acid substitutions (two encoded in TK and six in the DNA Pol gene) could be clarified. Between 1973 and 2014, the distribution of amino acid changes related to the natural gene polymorphisms of TK and DNA Pol remained largely stable. Resistance to ACV was confirmed phenotypically for 16 isolates, and resistance to ACV plus FOS was confirmed for 1 isolate. Acyclovir-resistant strains were observed from the year 1995 onwards, predominantly in immunosuppressed patients, especially those with stem cell transplantation, and the number of ACV-resistant strains increased during the last 2 decades. The data confirm the strong genetic variability among HIV-1 isolates, which is more pronounced in the DNA Pol gene than in the TK gene, and will facilitate considerably the rapid genotypic diagnosis of HSV-1 resistance.

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