1. Variability of UL18, UL40, UL111a and US3 immunomodulatory genes among human cytomegalovirus clinical isolates from renal transplant recipients
- Author
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Muriel Faure-Della Corte, Pierre Merville, Marie-Edith Lafon, Catherine Rio, Isabelle Garrigue, Noël Magnin, Julie Déchanet-Merville, Sophie Capdepont, Hervé Fleury, and Lionel Couzi
- Subjects
Male ,Human cytomegalovirus ,Genes, Viral ,Molecular Sequence Data ,Cytomegalovirus ,medicine.disease_cause ,Virus ,Herpesviridae ,Immediate-Early Proteins ,Viral Proteins ,Postoperative Complications ,Polymorphism (computer science) ,Betaherpesvirinae ,Virology ,Genetic variation ,medicine ,Humans ,Amino Acid Sequence ,Gene ,Phylogeny ,Glycoproteins ,biology ,Genetic Variation ,Membrane Proteins ,Middle Aged ,biology.organism_classification ,medicine.disease ,Kidney Transplantation ,Transplantation ,Infectious Diseases ,Cytomegalovirus Infections ,Immunology ,Capsid Proteins ,Female ,Sequence Alignment - Abstract
Background Variability of human cytomegalovirus (HCMV) genes counteracting immune responses is poorly investigated in non-cultured clinical strains. Objectives In HCMV-infected renal graft recipients, we aimed to (i) investigate the variability of four HCMV immunomodulatory genes, without any culture-related viral selection, (ii) provide evolutionary sequence data, and (iii) study co-existing HCMV variants and their evolution. Study design UL18, UL40, UL111a and US3 were sequenced in 31 blood samples from 17 patients (8 with sequential samples). Cloning of UL40 PCR products was performed in one donor-positive/recipient-positive (D+/R+) patient's samples. Results Each patient harboured a unique strain (combination of four genes), however single identical genes were demonstrated among various patients, suggesting recombination events. Sequencing showed in D+/R− recipients, either complete gene stability (four patients) or significant variability (one patient); in three D+/R+ patients, multiple gene variations, possibly linked to super- or co-infections. Cloning evidenced different variants at each time point with an increasing variability over time, illustrating possibly viral reactivations and the subsequent evolution of the variants mixture. Conclusion A noticeable HCMV natural polymorphism was shown, with different evolutive patterns. Moreover, we described the co-evolution of variants mixtures in one patient. Consequences on HCMV infection and graft function deserve further studying.
- Published
- 2007