The effect of (E)-5-(2-bromovinyl)-2'-deoxyuridine on DNA repair and mutagenesis of herpes simplex virus type 1

Virology. 1987 Nov;161(1):242-4. doi: 10.1016/0042-6822(87)90191-7.

Abstract

Growth of HSV-1 in (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) results in incorporation of the analog into HSV-1 DNA. Employing the technique of Weigle-type reactivation (WR), HSV-1 inactivated by uv irradiation but not by growth in BVDU is a substrate for induced cellular repair pathways. Growth of mammalian cells in BVDU does not induce cellular repair pathways detected by WR. HSV-1 temperature sensitive (ts) mutants demonstrate an increased reversion frequency to the nonpermissive phenotype (ts+) following growth in a high concentration of BVDU. A ts mutant did not display an increased reversion frequency following growth in equally inhibitory concentrations of an HSV-1 polymerase inhibitor, aphidicolin. These findings suggest that BVDU incorporated into HSV-1 DNA may not be readily excised and may be a mutagenic lesion in viral DNA, although other explanations are possible.

MeSH terms

  • Animals
  • Bromodeoxyuridine / analogs & derivatives*
  • Bromodeoxyuridine / metabolism
  • Bromodeoxyuridine / pharmacology
  • DNA Repair / drug effects*
  • DNA, Viral / drug effects*
  • DNA, Viral / metabolism
  • Genes, Viral
  • Mutation*
  • Simplexvirus / drug effects
  • Simplexvirus / genetics*
  • Simplexvirus / growth & development
  • Simplexvirus / radiation effects
  • Ultraviolet Rays
  • Vero Cells

Substances

  • DNA, Viral
  • brivudine
  • Bromodeoxyuridine