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 (HS V-1) infections occurred in a patient with Wiskott-Aldrich syndrome, an X-l inked recessive immunodeficiency syndrome composed of three clinical charac teristics of immunodeficiency, thrombocytopenia, and an eczematous dermatit is. The patient had severe and recurrent ACV-r herpes simplex and was treat ed 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 thymid ine kinase (TK) gene from these sequential ACV-r isolates was compared with the ACV-s isolates. A single nucleotide deletion of cytosine (C) from homo polymer 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 we re 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 ea ch 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 AC V-s strain in the patient body and that TK-associated ACV-r HSV-1 can react ivate from latency. J. Med. Virol. 58:387-393, 1999. (C) 1999 Wiley-Liss, I nc.