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

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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 (ACV^r) HSV-1 infection in the later phase of his life, especially after the episode of ACV^r HSV-1 infection. Virological analyses on the HSV-1 isolates recovered from this patient revealed that all the ACV^r 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^-/ACV^r HSV-1 infections throughout the patient's life were due to the identical ACV^r HSV-1 strain. Furthermore, it was found that the ACV-sensitive (ACV^s) isolate recovered from the skin lesions that appeared between the episodes of ACV^r infection at the ages of 8 and 9 contained ACV^r HSV-1 with the same mutation in the TK gene. These results indicate that, although TK activity is required for reactivation of TK⁺/ACV^s HSV-1 from latency and TK^-/ACV^r HSV-1 is unable to reactivate from latency, the TK^-/ACV^r HSV-1 strain isolated herein reactivated in this patient, possibly by using the TK activity induced by the latently co-infected TK⁺/ACV^s HSV-1.