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Inhibition of herpesvirus‐induced thymidine kinase and DNA polymerase by β‐hydroxynorvaline
Author(s) -
Massare Michael J.,
Blough Herbert A.
Publication year - 1987
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(87)80521-5
Subject(s) - dna polymerase , thymidine kinase , dna synthesis , dna replication , thymidine , biology , dna , microbiology and biotechnology , polymerase , dna polymerase ii , viral replication , dna polymerase delta , virology , dna clamp , virus , biochemistry , polymerase chain reaction , gene , herpes simplex virus , reverse transcriptase
Treatment of HSV‐infected cells with 5–10 mM β‐hydroxynorvaline (Hnv), a threonine analog, specifically affects herpesvirus DNA replication: both the rate of and total DNA synthesis are reduced, the former ∼ 15‐fold by Hnv (6 h post‐infection) and the latter by 12‐fold (between 3 and 12 h post‐infection). The effect on DNA replication was due to inhibition of HSV‐1 thymidine kinase (TK) and DNA polymerase (DP) activities; the former is reduced by 75% and whereas DP returns to baseline levels (when compared to untreated and/or uninfected cells). Host cell TK and DP activities are unaffected. It is suggested that β‐hydroxynorvaline is incorporated into these enzyme(s), either close to or at the active site thus perturbing viral DNA synthesis. β‐Hydroxynorvaline should have unique utility as a targeted antiviral compound, acting on both membrane‐mediated phenomena (fusion, penetration and attachment) and DNA replication.