title: 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 (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.
authors.affiliation: Department of Virology I, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shiota
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kurane
authors.forename: Shigeru
authors.initials: S
authors.lastname: Morikawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Saijo
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D006561:Herpes Simplex / Q000175:diagnosis* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D006801:Humans; D008297:Male; D012008:Recurrence; D017384:Sequence Deletion; D013937:Thymidine Kinase / Q000172:deficiency*; D014775:Virus Activation; D014923:Wiskott-Aldrich Syndrome / Q000150:complications*
chemical_list: D013937:Thymidine Kinase