title: Characterization of Human Cytomegalovirus Genome Diversity in Immunocompromised Hosts by Whole-Genome Sequencing Directly From Clinical Specimens.
abstract: Advances in next-generation sequencing (NGS) technologies allow comprehensive studies of genetic diversity over the entire genome of human cytomegalovirus (HCMV), a significant pathogen for immunocompromised individuals.
  
  
  
  Next-generation sequencing was performed on target enriched sequence libraries prepared directly from a variety of clinical specimens (blood, urine, breast milk, respiratory samples, biopsies, and vitreous humor) obtained longitudinally or from different anatomical compartments from 20 HCMV-infected patients (renal transplant recipients, stem cell transplant recipients, and congenitally infected children).
  
  
  
  De novo-assembled HCMV genome sequences were obtained for 57 of 68 sequenced samples. Analysis of longitudinal or compartmental HCMV diversity revealed various patterns: no major differences were detected among longitudinal, intraindividual blood samples from 9 of 15 patients and in most of the patients with compartmental samples, whereas a switch of the major HCMV population was observed in 6 individuals with sequential blood samples and upon compartmental analysis of 1 patient with HCMV retinitis. Variant analysis revealed additional aspects of minor virus population dynamics and antiviral-resistance mutations.
  
  
  
  In immunosuppressed patients, HCMV can remain relatively stable or undergo drastic genomic changes that are suggestive of the emergence of minor resident strains or de novo infection.
authors.affiliation: Institute of Virology.|German Centre for Infection Research, Hannover-Braunschweig, Germany.
authors.forename: Elias
authors.initials: E
authors.lastname: Hage
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, United Kingdom.
authors.forename: Gavin S
authors.initials: GS
authors.lastname: Wilkie
authors.affiliation: Department of Nephrology.
authors.forename: Silvia
authors.initials: S
authors.lastname: Linnenweber-Held
authors.affiliation: Institute of Virology.|German Centre for Infection Research, Hannover-Braunschweig, Germany.
authors.forename: Akshay
authors.initials: A
authors.lastname: Dhingra
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, United Kingdom.
authors.forename: Nicolás M
authors.initials: NM
authors.lastname: Suárez
authors.affiliation: Department of Nephrology.
authors.forename: Julius J
authors.initials: JJ
authors.lastname: Schmidt
authors.affiliation: Institute of Virology.|German Centre for Infection Research, Hannover-Braunschweig, Germany.
authors.forename: Penelope C
authors.initials: PC
authors.lastname: Kay-Fedorov
authors.affiliation: Department of Haematology, Haemostasis and Oncology, Hannover Medical School.|German Centre for Infection Research, Hannover-Braunschweig, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Mischak-Weissinger
authors.affiliation: Institute of Virology.|German Centre for Infection Research, Hannover-Braunschweig, Germany.
authors.forename: Albert
authors.initials: A
authors.lastname: Heim
authors.affiliation: Department of Nephrology.
authors.forename: Anke
authors.initials: A
authors.lastname: Schwarz
authors.affiliation: Institute of Virology.|German Centre for Infection Research, Hannover-Braunschweig, Germany.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Schulz
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Davison
authors.affiliation: Institute of Virology.|German Centre for Infection Research, Hannover-Braunschweig, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Ganzenmueller
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000145:classification / Q000235:genetics*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D016679:Genome, Viral / Q000235:genetics*; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016867:Immunocompromised Host; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D066027:Transplant Recipients
chemical_list: D004279:DNA, Viral
keywords: blood; evolution; genome diversity; human cytomegalovirus (HCMV); immunocompromised; next-generation sequencing; strain switch