Nucleotide Sequence of Thymidine Kinase Gene of Sequential Acyclovir-Resistant Herpes Simplex Virus Type 1 Isolates Recovered From a Child With Wiskott-Aldrich Syndrome: Evidence for Reactivation of Acyclovir-Resistant Herpes Simplex Virus

J Med Virol. 1999 Aug;58(4):387-93.


Recurrent acyclovir (ACV)-resistant (ACV-r) herpes simplex virus type 1 (HSV-1) infections occurred in a patient with Wiskott-Aldrich syndrome, an X-linked recessive immunodeficiency syndrome composed of three clinical characteristics of immunodeficiency, thrombocytopenia, and an eczematous dermatitis. The patient had severe and recurrent ACV-r herpes simplex and was treated with vidarabine in a satisfactory manner from 1993 to 1997. During the 4-year observation period, two ACV-sensitive (ACV-s) HSV-1 isolates and five ACV-r HSV-1 isolates were recovered. The nucleotide sequence of the thymidine kinase (TK) gene from these sequential ACV-r isolates was compared with the ACV-s isolates. A single nucleotide deletion of cytosine (C) from homopolymer stretch of four C residues between nucleotide 1061 and 1064 of the open reading frame was found in all ACV-r isolates. No other differences were observed in the TK nucleotide sequence between ACV-s and ACV-r isolates. The TK nucleotide sequences of the two ACV-s isolates were identical to each other and those of the five ACV-r isolates were identical to one another. These results suggest that the ACV-r HSV-1 might have derived from the ACV-s strain in the patient body and that TK-associated ACV-r HSV-1 can reactivate from latency.

Publication types

  • Case Reports

MeSH terms

  • Acyclovir / therapeutic use*
  • Amino Acid Sequence
  • Antiviral Agents / therapeutic use*
  • Base Sequence
  • Child
  • DNA, Viral / chemistry
  • DNA, Viral / genetics
  • Drug Resistance, Microbial
  • Follow-Up Studies
  • Genetic Variation
  • Herpes Simplex / complications
  • Herpes Simplex / virology*
  • Herpesvirus 1, Human / drug effects
  • Herpesvirus 1, Human / genetics*
  • Herpesvirus 1, Human / isolation & purification
  • Humans
  • Japan
  • Male
  • Microbial Sensitivity Tests
  • Molecular Sequence Data
  • Phosphorylation
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Thymidine Kinase / genetics*
  • Wiskott-Aldrich Syndrome / complications*


  • Antiviral Agents
  • DNA, Viral
  • Thymidine Kinase
  • Acyclovir