Long-term observation of herpes simplex virus type 1 (HSV-1) infection in a child with wiskott-aldrich syndrome and a possible reactivation mechanism for thymidine kinase-negative HSV-1 in humans

Abstract

Herpes simplex virus type 1 (HSV-1) infections in a child with congenital immunodeficiency syndrome were observed over a 10-year period. The child suffered from recurrent and severe HSV-1 mucocutaneous infections. He frequently suffered from acyclovir (ACV)-resistant (ACVr) HSV-1 infection in the later phase of his life, especially after the episode of ACVr HSV-1 infection. Virological analyses on the HSV-1 isolates recovered from this patient revealed that all the ACVr HSV-1 isolates were thymidine kinase (TK+)- negative (TK+-) due to a single cytosine (C) deletion within the 4-C residues (positions 1061 to 1064) in the TK+ gene, indicating that the recurrent TK+-/ACVr HSV-1 infections throughout the patient's life were due to the identical ACVr HSV-1 strain. Furthermore, it was found that the ACV-sensitive (ACVs) isolate recovered from the skin lesions that appeared between the episodes of ACVr infection at the ages of 8 and 9 contained ACVr HSV-1 with the same mutation in the TK+ gene. These results indicate that, although TK+ activity is required for reactivation of TK++/ACVs HSV-1 from latency and TK+-/ACVr HSV-1 is unable to reactivate from latency, the TK+-/ACVr HSV-1 strain isolated herein reactivated in this patient, possibly by using the TK+ activity induced by the latently co-infected TK++/ACVs HSV-1.