title: Analysis and clinical correlation of genetic variation in cytomegalovirus.
abstract: BACKGROUND
  Cytomegalovirus (CMV) displays genetic polymorphisms in multiple genes, which may result in important virulence differences. Glycoprotein N (gN) and immediate early 1 (IE1) are key viral genes and immune targets. We aimed to characterize the molecular epidemiology of gN and IE1 genotypes in organ transplant patients with CMV disease in the context of clinical and virologic endpoints.
  
  
  METHODS
  A total of 240 patients with CMV disease had genotyping analysis by nested polymerase chain reaction assays and sequencing using blood samples obtained at disease onset. Results were correlated with viral clearance kinetics and recurrence.
  
  
  RESULTS
  Complex patterns of gN and IE1 genotypes were present with no clear genetic linkages. No single genotype of IE1 or gN was associated with poorer outcome. For example, different gN or IE1 genotypes had comparable baseline viral load, clearance half-lives, time to clearance, and rates of virologic recurrence. Mixed infection was present at IE1 in 15.8% and gN in 21.9%, but analysis of a single gene was insufficient to detect all mixed infections. Infections caused by multiple strains, as opposed to single strains, were associated with higher baseline viral loads (P = 0.011), delayed viral clearance (P = 0.033), and higher rates of virologic recurrence (P = 0.008).
  
  
  CONCLUSIONS
  Genetic diversity in CMV is complex. Specific gN or IE subtypes do not seem to affect in vivo viral virulence patterns in single-strain infections. Mixed infections demonstrate associations with virologic outcomes that single-strain infections do not.
authors.affiliation: Transplant Infectious Diseases, University of Alberta, Edmonton, Alberta, Canada. lisboa@ualberta.ca
authors.forename: L F
authors.initials: LF
authors.lastname: Lisboa
authors.forename: Y
authors.initials: Y
authors.lastname: Tong
authors.forename: D
authors.initials: D
authors.lastname: Kumar
authors.forename: X L
authors.initials: XL
authors.lastname: Pang
authors.forename: A
authors.initials: A
authors.lastname: Asberg
authors.forename: A
authors.initials: A
authors.lastname: Hartmann
authors.forename: H
authors.initials: H
authors.lastname: Rollag
authors.forename: A G
authors.initials: AG
authors.lastname: Jardine
authors.forename: M D
authors.initials: MD
authors.lastname: Pescovitz
authors.forename: A
authors.initials: A
authors.lastname: Humar
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D003587:Cytomegalovirus / Q000235:genetics*; D003586:Cytomegalovirus Infections / Q000097:blood / Q000453:epidemiology / Q000209:etiology / Q000821:virology*; D015774:Ganciclovir / Q000031:analogs & derivatives / Q000627:therapeutic use; D014644:Genetic Variation; D005838:Genotype; D014943:Global Health; D006801:Humans; D017720:Molecular Epidemiology; D016377:Organ Transplantation / Q000009:adverse effects*; D000077562:Valganciclovir; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir