Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 215, Issue 11, Pages 1673-1683Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jix157
Keywords
next-generation sequencing; immunocompromised; human cytomegalovirus (HCMV); genome diversity; blood; strain switch; evolution
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Funding
- Deutsche Forschungsgemeinschaft Collaborative Research Centre 900 [SFB-900]
- German Center for Infection Research [TTU IICH 07 801]
- Volkswagen Foundation
- Communities Allied in Infection
- Medical Research Council [MC_UU_12014/3]
- graduate program Infection Biology of the Hannover Biomedical Research School
- MRC [MC_UU_12014/12, MC_UU_12014/3] Funding Source: UKRI
- Medical Research Council [MC_UU_12014/12, MC_UU_12014/3] Funding Source: researchfish
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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.
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