Characterization of Human Cytomegalovirus Genome Diversity in Immunocompromised Hosts by Whole-Genome Sequencing Directly From Clinical Specimens

J Infect Dis. 2017 Jun 1;215(11):1673-1683. doi: 10.1093/infdis/jix157.


Background: 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.

Methods: 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).

Results: 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.

Conclusions: 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.

Keywords: blood; evolution; genome diversity; human cytomegalovirus (HCMV); immunocompromised; next-generation sequencing; strain switch.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cohort Studies
  • Cytomegalovirus / classification
  • Cytomegalovirus / genetics*
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / virology*
  • DNA, Viral / analysis
  • DNA, Viral / genetics
  • Drug Resistance, Viral / genetics
  • Female
  • Genetic Variation / genetics
  • Genome, Viral / genetics*
  • Genomics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunocompromised Host*
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Transplant Recipients


  • DNA, Viral