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

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

Author information

1
Institute of Virology.
2
German Centre for Infection Research, Hannover-Braunschweig, Germany.
3
MRC-University of Glasgow Centre for Virus Research, United Kingdom.
4
Department of Nephrology.
5
Department of Haematology, Haemostasis and Oncology, Hannover Medical School.

Abstract

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

Comment in

PMID:
28368496
DOI:
10.1093/infdis/jix157
[Indexed for MEDLINE]

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