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.
Prix
L
L
Department of Medical Virology and Epidemiology of Viral Diseases, University Hospital of Tübingen, 72076 Tübingen, Germany. lothar. prix@med.uni-tuebingen.de
Hamprecht
K
K
Holzhüter
B
B
Handgretinger
R
R
Klingebiel
T
T
Jahn
G
G
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