Multiple-strain infections of human cytomegalovirus with high genomic diversity are common in breast milk from human immunodeficiency virus-infected women in Zambia

Suárez, N. M., Musonda, K. G., Escriva, E., Njenga, M., Agbueze, A., Camiolo, S. , Davison, A. J. and Gompels, U. A. (2019) Multiple-strain infections of human cytomegalovirus with high genomic diversity are common in breast milk from human immunodeficiency virus-infected women in Zambia. Journal of Infectious Diseases, 220(5), pp. 792-801. (doi:10.1093/infdis/jiz209) (PMID:31050737) (PMCID:PMC6667993)

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Abstract

Background: In developed countries, human cytomegalovirus (HCMV) is a major pathogen in congenitally infected and immunocompromised individuals, where multiple-strain infection appears linked to disease severity. The situation is less documented in developing countries. In Zambia, breast milk is a key route for transmitting HCMV and carries higher viral loads in human immunodeficiency virus (HIV)–infected women. We investigated HCMV strain diversity. Methods: High-throughput sequence datasets were generated from 28 HCMV-positive breast milk samples donated by 22 mothers (15 HIV-infected and 7 HIV-negative) at 4–16 weeks postpartum, then analyzed by genome assembly and novel motif-based genotyping in 12 hypervariable HCMV genes. Results: Among the 20 samples from 14 donors (13 HIV-infected and one HIV-negative) who yielded data meeting quality thresholds, 89 of the possible 109 genotypes were detected, and multiple-strain infections involving up to 5 strains per person were apparent in 9 HIV-infected women. Strain diversity was extensive among individuals but conserved compartmentally and longitudinally within them. Genotypic linkage was maintained within hypervariable UL73/UL74 and RL12/RL13/UL1 loci for virus entry and immunomodulation, but not between genes more distant from each other. Conclusions: Breast milk from HIV-infected women contains multiple HCMV strains of high genotypic complexity and thus constitutes a major source for transmitting viral diversity.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Davison, Professor Andrew and Suarez, Dr Nicolas and Camiolo, Dr Salvatore
Authors: Suárez, N. M., Musonda, K. G., Escriva, E., Njenga, M., Agbueze, A., Camiolo, S., Davison, A. J., and Gompels, U. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Infectious Diseases
Publisher:Oxford University Press
ISSN:0022-1899
ISSN (Online):1537-6613
Published Online:03 May 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Journal of Infectious Diseases 220(5):792-801
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
738561Exploiting a human challenge model to understand the pathogenesis of cytomegalovirusAndrew DavisonWellcome Trust (WELLCOTR)204870/Z/16/ZMVLS III - CENTRE FOR VIRUS RESEARCH

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