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.
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 HCMVinfection and graft function deserve further studying.
Authors: Susan L Heatley; Gabriella Pietra; Jie Lin; Jacqueline M L Widjaja; Christopher M Harpur; Sue Lester; Jamie Rossjohn; Jeff Szer; Anthony Schwarer; Kenneth Bradstock; Peter G Bardy; Maria Cristina Mingari; Lorenzo Moretta; Lucy C Sullivan; Andrew G Brooks Journal: J Biol Chem Date: 2013-01-18 Impact factor: 5.157
Authors: Naomi J Logsdon; Meghan K Eberhardt; Christopher E Allen; Peter A Barry; Mark R Walter Journal: PLoS One Date: 2011-11-21 Impact factor: 3.240
Authors: Steven Sijmons; Kim Thys; Michaël Corthout; Ellen Van Damme; Marnix Van Loock; Stefanie Bollen; Sylvie Baguet; Jeroen Aerssens; Marc Van Ranst; Piet Maes Journal: PLoS One Date: 2014-04-22 Impact factor: 3.240
Authors: Andrea R McWhorter; Lee M Smith; Laura L Masters; Baca Chan; Geoffrey R Shellam; Alec J Redwood Journal: PLoS Pathog Date: 2013-01-03 Impact factor: 6.823