Human cytomegalovirus multiple-strain infections and viral population diversity in haematopoietic stem cell transplant recipients analysed by high-throughput sequencing

Dhingra, A. et al. (2021) Human cytomegalovirus multiple-strain infections and viral population diversity in haematopoietic stem cell transplant recipients analysed by high-throughput sequencing. Medical Microbiology and Immunology, 210(5-6), pp. 291-304. (doi: 10.1007/s00430-021-00722-5) (PMID:34611744) (PMCID:PMC8541999)

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Abstract

Human cytomegalovirus (HCMV) is an important opportunistic pathogen in allogeneic haematopoietic stem cell transplant (HSCT) recipients. High-throughput sequencing of target-enriched libraries was performed to characterise the diversity of HCMV strains present in this high-risk group. Forty-four HCMV-DNA-positive plasma specimens (median viral input load 321 IU per library) collected at defined time points from 23 HSCT recipients within 80 days of transplantation were sequenced. The genotype distribution for 12 hypervariable HCMV genes and the number of HCMV strains present (i.e. single- vs. multiple-strain infection) were determined for 29 samples from 16 recipients. Multiple-strain infection was observed in seven of these 16 recipients, and five of these seven recipients had the donor (D)/recipient (R) HCMV-serostatus combination D + R + . A very broad range of genotypes was detected, with an intrahost composition that was generally stable over time. Multiple-strain infection was not associated with particular virological or clinical features, such as altered levels or duration of antigenaemia, development of acute graft-versus-host disease or increased mortality. In conclusion, despite relatively low viral plasma loads, a high frequency of multiple-strain HCMV infection and a high strain complexity were demonstrated in systematically collected clinical samples from this cohort early after HSCT. However, robust evaluation of the pathogenic role of intrahost viral diversity and multiple-strain infection will require studies enrolling larger numbers of recipients.

Item Type:Articles
Additional Information:Open Access funding enabled and organized by Projekt DEAL. This work was supported by the Deutsche Forschungsgemeinschaft (DFG) Collaborative Research Centre (SFB) 900, core project Z1 [Grant number SFB-900, Z1], the German Center for Infection Research (DZIF) [Grant number TTU IICH 07 801] and the Medical Research Council [grant number MC_UU_12014/3]. A. Dhingra and J. Götting were supported by the graduate programme “Infection Biology” of the Hannover Biomedical Research School (HBRS). S. Camiolo was supported by the Wellcome Trust (WT) [Grant number 204870/Z/16/Z].
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Camiolo, Dr Salvatore and Suarez, Dr Nicolas and Davison, Professor Andrew
Authors: Dhingra, A., Götting, J., Varanasi, P. R., Steinbrueck, L., Camiolo, S., Zischke, J., Heim, A., Schulz, T. F., Weissinger, E. M., Kay-Fedorov, P., Davison, A., Suarez, N., and Ganzenmuller, T.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Medical Microbiology and Immunology
Publisher:Springer
ISSN:0300-8584
ISSN (Online):1432-1831
Published Online:06 October 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Medical Microbiology and Immunology 210(5-6): 291-304
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656321Genomics of human cytomegalovirusAndrew DavisonMedical Research Council (MRC)MC_UU_12014/3MVLS III - CENTRE FOR VIRUS RESEARCH
174258Exploiting a human challenge model to understand the pathogenesis of cytomegalovirusAndrew DavisonWellcome Trust (WELLCOTR)204870/Z/16/Z (17/0008)III-MRC-GU Centre for Virus Research