UL40 human cytomegalovirus variability evolution patterns over time in renal transplant recipients.
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.
Garrigue
Isabelle
I
Université Bordeaux 2, Laboratoire de Virologie EA2968 and IFR66, F-33 076 Bordeaux, France. isabelle.garrigue@chu-bordeaux.fr
Faure-Della Corte
Muriel
M
Magnin
Noël
N
Recordon-Pinson
Patricia
P
Couzi
Lionel
L
Lebrette
Marie-Elise
ME
Schrive
Marie-Hélène
MH
Roncin
Loïc
L
Taupin
Jean-Luc
JL
Déchanet-Merville
Julie
J
Fleury
Hervé
H
Lafon
Marie-Edith
ME
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*
D000998:Antiviral Agents; C404228:UL40 glycoprotein, Cytomegalovirus; D014764:Viral Proteins; D015774:Ganciclovir