Intracellular uptake of thymidine and antiherpetic drugs for thymidine kinase-deficient mutants of herpes simplex virus type 1

Pan Kee Bae, Jee Hyun Kim, Hae Soo Kim, In Kwon Chung, Sang Gi Paik, Chong Kyo Lee

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

The influence of the thymidine (Thd) kinase (TK) of herpes simplex virus type 1 (HSV-1) on the intracellular uptake and anabolism of nucleosides has been investigated. To compare the differences between the TK-positive (TK+) and TK-deficient strains, acyclovir (ACV)-resistant strains were cloned from a cell culture and classified into 2 groups, viz. the TK-partial (TKp) and TK-negative (TK-). The cellular uptake of thymidine was highly dependent on the viral TK (vTK) activity. The TK+ strain showed the highest level of intracellular thymidine uptake, the TKp strain a moderate level, which varied from strain to strain, and the TK- and mock strains showed little uptake. The inhibition of viral replication by ACV, ganciclovir (GCV) and penciclovir (PCV) did not decrease the Thd uptake at all. On the contrary, a notable increase found to be induced by ACV. The influence of the vTK on the uptake of GCV or PCV was much greater than that of ACV. The metabolism was generally less dependent on the vTK activity than the influx. The influx and phosphorylation rates of GCV and PCV were dependent on the substrate specificity of the vTK.

Original languageEnglish
Pages (from-to)93-104
Number of pages12
JournalAntiviral Research
Volume70
Issue number3
DOIs
Publication statusPublished - 2006 Jul

Bibliographical note

Funding Information:
We are grateful to the former SmithKline Beecham Pharmaceuticals for providing penciclovir. This work was supported by grant number M1-0106-00-0102 from the Ministry of Science and Technology of Korea.

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Virology

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