About: Impact of novel mutations of herpes simplex virus 1 and 2 thymidine kinases on acyclovir phosphorylation activity     Goto   Sponge   NotDistinct   Permalink

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Description
  • The acyclic analogue of guanosine acyclovir (ACV) constitutes the first-line drug for the treatment of herpes simplex virus (HSV) infections. ACV activation requires primophosphorylation by virus-encoded HSV thymidine kinase (TK). In 95% of cases, HSV resistance to ACV is associated with mutations located in TK. The aim of this work was to address the question of the potential involvement of novel HSV-1 and HSV-2 TK mutations in reduced susceptibility to ACV using a novel nonradioactive method, based on luminescent quantitation of ADP, for the evaluation of in vitro phosphorylation activity of TK. All recombinant TKs tested exhibited significantly lower ACV phosphorylation activities in comparison with those of reference KOS or gHSV-2 TKs (p < 0.015), therefore indicating that amino acid changes Y53D, L170P, R176W, A207P (HSV-1) and S66P, A725, I101S, M183I (HSV-2) were likely to be involved in HSV resistance to ACV.
  • The acyclic analogue of guanosine acyclovir (ACV) constitutes the first-line drug for the treatment of herpes simplex virus (HSV) infections. ACV activation requires primophosphorylation by virus-encoded HSV thymidine kinase (TK). In 95% of cases, HSV resistance to ACV is associated with mutations located in TK. The aim of this work was to address the question of the potential involvement of novel HSV-1 and HSV-2 TK mutations in reduced susceptibility to ACV using a novel nonradioactive method, based on luminescent quantitation of ADP, for the evaluation of in vitro phosphorylation activity of TK. All recombinant TKs tested exhibited significantly lower ACV phosphorylation activities in comparison with those of reference KOS or gHSV-2 TKs (p < 0.015), therefore indicating that amino acid changes Y53D, L170P, R176W, A207P (HSV-1) and S66P, A725, I101S, M183I (HSV-2) were likely to be involved in HSV resistance to ACV. (en)
Title
  • Impact of novel mutations of herpes simplex virus 1 and 2 thymidine kinases on acyclovir phosphorylation activity
  • Impact of novel mutations of herpes simplex virus 1 and 2 thymidine kinases on acyclovir phosphorylation activity (en)
skos:prefLabel
  • Impact of novel mutations of herpes simplex virus 1 and 2 thymidine kinases on acyclovir phosphorylation activity
  • Impact of novel mutations of herpes simplex virus 1 and 2 thymidine kinases on acyclovir phosphorylation activity (en)
skos:notation
  • RIV/00064203:_____/12:8269!RIV13-MZ0-00064203
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • I
http://linked.open...iv/cisloPeriodika
  • 3
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
http://linked.open.../riv/druhVysledku
http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 140665
http://linked.open...ai/riv/idVysledku
  • RIV/00064203:_____/12:8269
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • Herpes simplex virus; Thymidine kinase; Acyclovir phosphorylation activity; Nonradioactive method; genotypic characterization; dna-polymerase; phenotypic characterization; antiviral drugs; genetic content; resistant; type-1; transplantation; polymorphism; mutagenesis (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • NL - Nizozemsko
http://linked.open...ontrolniKodProRIV
  • [A8B5EE8C2F5C]
http://linked.open...i/riv/nazevZdroje
  • Antiviral Research
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 96
http://linked.open...iv/tvurceVysledku
  • Hubáček, Petr
  • Agut, H.
  • Bonnafous, P.
  • Boutolleau, D.
  • Burrel, S.
http://linked.open...ain/vavai/riv/wos
  • 000312518100014
issn
  • 0166-3542
number of pages
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