title: UL40 human cytomegalovirus variability evolution patterns over time in renal transplant recipients.
abstract: BACKGROUND
  Human cytomegalovirus (HCMV) is the most common opportunistic pathogen infecting immunocompromised patients after transplantation. Although its immunomodulatory capacities and genomic variability participate in immune system evasion, they are poorly studied in clinical strains without culture amplification. One of HCMV immunomodulatory genes, UL40, confers HCMV-infected cells' protection from natural killer-mediated lysis through its encoded nonapeptide presented in the context of human leukocyte antigen-E.
  
  
  METHODS
  In three renal transplant recipients with different HCMV serostatus, we aimed to evidence the co-evolution of mixtures of HCMV variants over time with sequencing and cloning of HCMV UL40 gene.
  
  
  RESULTS
  Six months after renal transplantation in patient 1Bx, D+/R+, UL40 phylogenetic and bootscan analysis suggested the emergence of a recombination between two previous viral strains. In patient 8Bx, initially D+/R-, distribution of variants in five samples over 43 months was notably stable, with no visible emerging variants despite two renal engraftments and extended episodes of active infection. In patient 9Bx, also D+/R-, phylogenetic tree of viral variants revealed in the first sample a minor clone, confirmed by a specific polymerase chain reaction, related to the three subsequent dominant clones.
  
  
  CONCLUSIONS
  In three HCMV-infected renal transplant recipients, we have evidenced different viral evolutive polymorphisms including point mutations, recombination, and occasionally suggesting the intervention of several HCMV strains or a quasispecies-like distribution. This variability could contribute to viral adaptability in pathogenesis.
authors.affiliation: Université Bordeaux 2, Laboratoire de Virologie EA2968 and IFR66, F-33 076 Bordeaux, France. isabelle.garrigue@chu-bordeaux.fr
authors.forename: Isabelle
authors.initials: I
authors.lastname: Garrigue
authors.forename: Muriel
authors.initials: M
authors.lastname: Faure-Della Corte
authors.forename: Noël
authors.initials: N
authors.lastname: Magnin
authors.forename: Patricia
authors.initials: P
authors.lastname: Recordon-Pinson
authors.forename: Lionel
authors.initials: L
authors.lastname: Couzi
authors.forename: Marie-Elise
authors.initials: ME
authors.lastname: Lebrette
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Schrive
authors.forename: Loïc
authors.initials: L
authors.lastname: Roncin
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Taupin
authors.forename: Julie
authors.initials: J
authors.lastname: Déchanet-Merville
authors.forename: Hervé
authors.initials: H
authors.lastname: Fleury
authors.forename: Marie-Edith
authors.initials: ME
authors.lastname: Lafon
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D003587:Cytomegalovirus / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000235:genetics / Q000517:prevention & control; D019143:Evolution, Molecular; D005500:Follow-Up Studies; D015774:Ganciclovir / Q000031:analogs & derivatives / Q000627:therapeutic use; D014644:Genetic Variation; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D010802:Phylogeny; D012086:Reoperation; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D000998:Antiviral Agents; C404228:UL40 glycoprotein, Cytomegalovirus; D014764:Viral Proteins; D015774:Ganciclovir