Abstract

BackgroundIn 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.MethodsHigh-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.ResultsAmong 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.ConclusionsBreast milk from HIV-infected women contains multiple HCMV strains of high genotypic complexity and thus constitutes a major source for transmitting viral diversity.

Highlights

  • 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

  • High-throughput sequence datasets were generated from 28 HCMV-positive breast milk samples donated by 22 mothers (15 human immunodeficiency virus (HIV)-infected and 7 HIV-negative) at 4–16 weeks postpartum, analyzed by genome assembly and novel motifbased genotyping in 12 hypervariable HCMV genes

  • Human cytomegalovirus (HCMV) is a major coinfection in human immunodeficiency virus (HIV)–infected people, in whom, as in other immunocompromised individuals such as transplant recipients, it contributes to morbidity and mortality

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Summary

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, analyzed by genome assembly and novel motifbased genotyping in 12 hypervariable HCMV genes. Anonymized breast milk samples were collected with informed consent as a substudy of the Breast Feeding and Postpartum Health study conducted at the University Teaching Hospital, Lusaka, Zambia, as approved by the ethical committees of the University Teaching Hospital and the London School of Hygiene and Tropical Medicine. Donora HIV Status Breast Sample Weeks Postpartum

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