title: Impact of genetic polymorphisms in cytomegalovirus glycoprotein B on outcomes in solid-organ transplant recipients with cytomegalovirus disease.
abstract: BACKGROUND
  It is unknown whether specific viral polymorphisms affect in vivo therapeutic response in patients with cytomegalovirus (CMV) disease. Polymorphisms in the CMV glycoprotein B (gB) gene allow discrimination of 4 distinct genotypes (gB1-gB4). We assessed the influence of gB genotypes on the clinical and virologic outcome of CMV disease.
  
  
  METHODS
  Solid-organ transplant recipients enrolled in a multicenter trial of CMV disease treatment (VICTOR study) were included in this study. CMV gB genotyping was performed using quantitative real-time polymerase chain reaction at day 0 (start of antiviral therapy).
  
  
  RESULTS
  Among 239 patients with CMV disease, the prevalence of gB strain types was 26% for gB1, 10% for gB2, 10% for gB3, and 5% for gB4, whereas mixed infections were present in 49%. Donor-seropositive/recipient-seropositive patients were more likely to have mixed gB infection than donor-seropositive/recipient-seronegative patients (40% vs. 12%; P = .001). Median baseline viral loads were higher and time to viral eradication was longer ( P = .006 and P = .026 , respectively) for mixed infection versus infection with a single genotype. In a multivariate model, mixed gB infection was a significant predictor of failure to eradicate virus by day 21 (mixed vs single genotype; odds ratio, 2.66; 95% confidence interval, 1.31-5.38; P = .007 ) after controlling for baseline viral load, CMV serostatus at baseline, ganciclovir resistance, and antiviral treatment. No effect of gB genotype was seen on virologic or clinical CMV recurrence.
  
  
  CONCLUSIONS
  No specific gB genotype appears to confer a specific CMV virulence advantage. However, mixed gB genotype infections are associated with higher viral loads and delayed viral clearance.
authors.affiliation: Transplant Infectious Diseases and Provincial Laboratory for Public Health (Microbiology), University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Oriol
authors.initials: O
authors.lastname: Manuel
authors.forename: Anders
authors.initials: A
authors.lastname: Asberg
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Pang
authors.forename: Halvor
authors.initials: H
authors.lastname: Rollag
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Emery
authors.forename: Jutta K
authors.initials: JK
authors.lastname: Preiksaitis
authors.forename: Deepali
authors.initials: D
authors.lastname: Kumar
authors.forename: Mark D
authors.initials: MD
authors.lastname: Pescovitz
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Bignamini
authors.forename: Anders
authors.initials: A
authors.lastname: Hartmann
authors.forename: Alan G
authors.initials: AG
authors.lastname: Jardine
authors.forename: Atul
authors.initials: A
authors.lastname: Humar
mesh_terms: D000328:Adult; D003587:Cytomegalovirus / Q000235:genetics* / Q000472:pathogenicity*; D003586:Cytomegalovirus Infections / Q000821:virology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects*; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011183:Postoperative Complications / Q000821:virology; D012008:Recurrence; D012720:Severity of Illness Index; D014759:Viral Envelope Proteins / Q000235:genetics*; D019562:Viral Load; D014774:Virulence
chemical_list: D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus