Bone marrow transplantation in a child with Wiskott-Aldrich syndrome latently infected with acyclovir-resistant (ACV(r)) herpes simplex virus type 1: emergence of foscarnet-resistant virus originating from the ACV(r) virus.
A human leukocyte antigen (HLA)-matched unrelated bone marrow transplantation (BMT) was performed in a 13-year-old patient with the congenital immunodeficiency syndrome, Wiskott-Aldrich syndrome. The patient had a history of acyclovir (ACV)-resistant (ACV(r)) herpes simplex virus type 1 (HSV-1) infections prior to BMT. After BMT, the skin lesions caused by HSV-1 relapsed on the face and genito-anal areas. Ganciclovir (GCV) therapy was initiated, but the mucocutaneous lesions worsened. An HSV-1 isolate recovered from the lesions during this episode was resistant to both ACV and GCV. The ACV(r) isolate was confirmed to have the same mutation in the viral thymidine kinase (TK) gene as that of the previously isolated ACV(r) isolates from the patient. After treatment switch to foscarnet (PFA), there was a satisfactory remission but not a complete recovery. Although the mucocutaneous lesions improved, a PFA-resistant (PFA(r)) HSV-1 was isolated 1 month after the start of PFA therapy. The PFA(r) HSV-1 isolate coded for the same mutation in the viral TK gene as the ACV(r) HSV-1 isolates. Furthermore, the PFA(r) isolate also expressed a mutated viral DNA polymerase (DNA pol) with an amino acid (Gly) substitution for Val at position 715. This is the first report on the clinical course of a BMT-associated ACV(r) HSV-1 infection that subsequently developed resistance to foscarnet as well.
Saijo
Masayuki
M
Special Pathogens Laboratory, Department of Virology 1, National Institute of Infectious Diseases, Tokyo, Japan. msaijo@nih.go.jp
Yasuda
Yukiharu
Y
Yabe
Hiromasa
H
Kato
Shunichi
S
Suzutani
Tatsuo
T
De Clercq
Erik
E
Niikura
Masahiro
M
Maeda
Akihiko
A
Kurane
Ichiro
I
Morikawa
Shigeru
S
D000212:Acyclovir / Q000494:pharmacology*; D000293:Adolescent; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D016026:Bone Marrow Transplantation; D002460:Cell Line; D002522:Chlorocebus aethiops; D004279:DNA, Viral; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D024882:Drug Resistance, Viral; D017245:Foscarnet / Q000494:pharmacology*; D006561:Herpes Simplex / Q000150:complications / Q000503:physiopathology / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D013937:Thymidine Kinase / Q000235:genetics; D014709:Vero Cells; D017735:Virus Latency; D014923:Wiskott-Aldrich Syndrome / Q000150:complications / Q000821:virology*
D000998:Antiviral Agents; D004279:DNA, Viral; D018894:Reverse Transcriptase Inhibitors; D017245:Foscarnet; D013937:Thymidine Kinase; D004259:DNA-Directed DNA Polymerase; D000212:Acyclovir