Comprehensive restriction analysis of the UL97 region allows early detection of ganciclovir-resistant human cytomegalovirus in an immunocompromised child.
Children with innate immunodeficiencies may be at high risk for early development of ganciclovir-resistant human cytomegalovirus (HCMV) infection after bone marrow transplantation (BMT). For early and frequent monitoring of the occurrence of ganciclovir resistance-associated mutations in codons of the UL97 gene, a panel of previously described restriction assays was expanded for use on codons 591, 592, and 603. This technique enabled detection of suddenly emerging ganciclovir-resistant HCMV after BMT in a 7-year-old child with a T cell defect. Resistance emerged among the isolation of a ganciclovir-sensitive HCMV strain 32 days after transplantation, the first detection of genotypical resistance at day 44, and the isolation of resistant HCMV (ID50>12 microM) at day 54. Simple and yet comprehensive methods for therapy surveillance may be important in this patient group, in which the restriction assays proved useful.
Department of Medical Virology and Epidemiology of Viral Diseases, University Hospital of Tübingen, 72076 Tübingen, Germany. lothar. prix@med.uni-tuebingen.de
L
L
Prix
K
K
Hamprecht
B
B
Holzhüter
R
R
Handgretinger
T
T
Klingebiel
G
G
Jahn
D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002675:Child, Preschool; D003062:Codon; D003587:Cytomegalovirus / Q000187:drug effects* / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D004352:Drug Resistance, Microbial / Q000235:genetics; D015774:Ganciclovir / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length; D015183:Restriction Mapping; D017422:Sequence Analysis, DNA
D000998:Antiviral Agents; D003062:Codon; D004279:DNA, Viral; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D015774:Ganciclovir