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.
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.
Department of Pediatrics, Asahikawa Medical College, Hokkaido, Japan. msaijo@nih.go.jp
M
M
Saijo
T
T
Suzutani
K
K
Itoh
Y
Y
Hirano
K
K
Murono
M
M
Nagamine
K
K
Mizuta
M
M
Niikura
S
S
Morikawa
D000212:Acyclovir / Q000627:therapeutic use*; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000627:therapeutic use*; D001483:Base Sequence; D002648:Child; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D004352:Drug Resistance, Microbial; D005500:Follow-Up Studies; D014644:Genetic Variation; D006561:Herpes Simplex / Q000150:complications / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007564:Japan; D008297:Male; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013937:Thymidine Kinase / Q000235:genetics*; D014923:Wiskott-Aldrich Syndrome / Q000150:complications*
D000998:Antiviral Agents; D004279:DNA, Viral; D013937:Thymidine Kinase; D000212:Acyclovir