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

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.

scholarly journals Antiviral activity of the 3′;-amino derivative of (E)-5-(2-bromovinyl)-2′;-deoxyuridine

1983 ◽  
Vol 211 (2) ◽  
pp. 439-445 ◽  
Author(s):  
E De Clercq ◽  
J Descamps ◽  
J Balzarini ◽  
T Fukui ◽  
H S Allaudeen
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Thymidine Kinase ◽  
Dna Polymerase ◽  
Dna Polymerases ◽  
Amino Derivative ◽  
Dna Polymerase Alpha ◽  
Simplex Virus ◽  
Hsv 1

3′-NH2-BV-dUrd, the 3′-amino derivative of (E)-5-(2-bromovinyl)-2′-deoxyuridine, was found to be a potent and selective inhibitor of herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV) replication. 3′-NH2-BV-dUrd was about 4-12 times less potent but equally selective in its anti-herpes activity as BV-dUrd. Akin to BV-dUrd, 3′-NH2-BV-dUrd was much less inhibitory to herpes simplex virus type 2 than type 1. It was totally inactive against a thymidine kinase-deficient mutant of HSV-1. The 5′-triphosphate of 3′-NH2-BV-dUrd (3′-NH2-BV-dUTP) was evaluated for its inhibitory effects on purified herpes viral and cellular DNA polymerases. Among the DNA polymerases tested, HSV-1 DNA polymerase and DNA polymerase alpha were the most sensitive to inhibition by 3′-NH2-BV-dUTP (Ki values 0.13 and 0.10 microM, respectively). The Km/Ki ratio for DNA polymerase alpha was 47, as compared with 4.6 for HSV-1 DNA polymerase. Thus, the selectivity of 3′-NH2-BV-dUrd as an anti-herpes agent cannot be ascribed to a discriminative effect of its 5′-triphosphate at the DNA polymerase level. This selectivity most probably resides at the thymidine kinase level. 3′;-NH2-BV-dUrd would be phosphorylated preferentially by the HSV-1-induced thymidine kinase (Ki 1.9 microM, as compared with greater than 200 microM for the cellular thymidine kinase), and this preferential phosphorylation would confine the further action of the compound to the virus-infected cell.

In vitro isolation of variants of herpes simplex virus attenuated with altered thymidine kinase and DNA polymerase genes using carrageenans as selection agents

Symbiosis ◽  
2016 ◽  
Vol 72 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Cecilia G. Mateu ◽  
María C. Artuso ◽  
Carlos A. Pujol ◽  
Florencia N. Linero ◽  
Luis A. Scolaro ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Thymidine Kinase ◽  
Dna Polymerase ◽  
Simplex Virus

scholarly journals 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

2015 ◽  
Vol 71 (1) ◽  
pp. 6-16 ◽  
Author(s):  
Andreas Sauerbrei ◽  
Kathrin Bohn-Wippert ◽  
Marisa Kaspar ◽  
Andi Krumbholz ◽  
Matthias Karrasch ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Thymidine Kinase ◽  
Dna Polymerase ◽  
Synonymous Mutations ◽  
Simplex Virus
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