title: Emergence and compartmentalization of fatal multi-drug-resistant cytomegalovirus infection in a patient with autosomal-recessive severe combined immune deficiency.
abstract: The authors describe a patient with autosomal-recessive severe combined immunodeficiency (SCID) with severe, multiorgan cytomegalovirus (CMV) disease. In the face of appropriate therapy, the patient developed a 100-fold gradient in viral load across the blood-brain barrier. Disseminated disease, including pneumonitis, contributed to a fatal outcome. Serial genotypic analyses revealed multiple UL97 and UL54 (DNA polymerase) mutations that conferred phenotypic resistance to all currently licensed systemic CMV antivirals.
authors.affiliation: Pediatric Residency Training Program, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Blackman
authors.forename: Nell S
authors.initials: NS
authors.lastname: Lurain
authors.forename: David P
authors.initials: DP
authors.lastname: Witte
authors.forename: Alexandra H
authors.initials: AH
authors.lastname: Filipovich
authors.forename: Pam
authors.initials: P
authors.lastname: Groen
authors.forename: Mark R
authors.initials: MR
authors.lastname: Schleiss
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D002451:Cell Compartmentation; D002869:Chromosome Aberrations; D003587:Cytomegalovirus / Q000187:drug effects / Q000302:isolation & purification* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D024921:Drug Resistance, Multiple, Viral; D017809:Fatal Outcome; D005808:Genes, Recessive; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D016133:Polymerase Chain Reaction; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000821:virology*; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; C109367:UL54 protein, Human herpesvirus 5; D014764:Viral Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D004259:DNA-Directed DNA Polymerase