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- Title
Characterization of Human Cytomegalovirus Genome Diversity in Immunocompromised Hosts by Whole-Genome Sequencing Directly From Clinical Specimens.
- Authors
Hage, Elias; Wilkie, Gavin S.; Linnenweber-Held, Silvia; Dhingra, Akshay; Suárez, Nicolás M.; Schmidt, Julius J.; Kay-Fedorov, Penelope C.; Mischak-Weissinger, Eva; Heim, Albert; Schwarz, Anke; Schulz, Thomas F.; Davison, Andrew J.; Ganzenmueller, Tina; Hage, E; Wilkie, G S; Linnenweber-Held, S; Dhingra, A; Suárez, N M; Schmidt, J J; Kay-Fedorov, P
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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).<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
GENOMES; CYTOMEGALOVIRUSES; HUMAN cytomegalovirus; HUMAN cytomegalovirus diseases; BIOPSY; DNA analysis; CYTOMEGALOVIRUS diseases; DNA; DRUG resistance in microorganisms; GENETICS; LONGITUDINAL method; RESEARCH funding; TRANSPLANTATION of organs, tissues, etc.; GENOMICS; IMMUNOCOMPROMISED patients; SEQUENCE analysis
- Publication
Journal of Infectious Diseases, 2017, Vol 215, Issue 11, p1673
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jix157