Mixed cytomegalovirus genotypes in HIV positive mothers show compartmentalization and distinct patterns of transmission to infants
- University College London, United Kingdom
- University of Washington, United States
- University College of London, United Kingdom
- University of Nairobi, Kenya
- University of Montréal, Canada
Abstract
Cytomegalovirus (CMV) is the commonest cause of congenital infection (cCMVi) and particularly so among infants born to HIV-infected women. Studies of cCMVi pathogenesis are complicated by the presence of multiple infecting maternal CMV strains, especially in HIV-positive women, and the large, recombinant CMV genome. Using newly developed tools to reconstruct CMV haplotypes, we demonstrate anatomic CMV compartmentalization in five HIV-infected mothers and identify the possibility of congenitally transmitted genotypes in three of their infants. A single CMV strain was transmitted in each congenitally infected case, and all were closely related to those that predominate in the cognate maternal cervix. Compared to non-transmitted strains, these congenitally transmitted CMV strains showed statistically significant similarities in 19 genes associated with tissue-tropism and immunomodulation. In all infants, incident superinfections with distinct strains from breast milk were captured during follow-up. The results represent potentially important new insights into the virologic determinants of early CMV infection.
Data availability
Sequence reads have been deposited in NCBI Sequence Read Archive under BioProject ID PRJNA605798.
Article and author information
Author details
Richard A Goldstein
Funding
EUFP7 (304875)
- Judith Breuer
UCL/UCLH NIHR Biomedical Research Centre
- Judith Breuer
Sir Henry Wellcome Fellowship
- Sofia Morfopoulou
Sir Henry Wellcome Fellowships
- Josephine Bryant
Wellcome Trust (204870)
- Paul Griffiths
NIH National Institute of Allergy and Infectious Diseases (AI087369)
- Jennifer A Slyker
NIH National Institute of Allergy and Infectious Diseases (AI027757)
- Jennifer A Slyker
NIH National Institute of Allergy and Infectious Diseases (AI076105)
- Carey Farquhar
NIH National Institute of Allergy and Infectious Diseases (AI087399)
- Carey Farquhar
National Institute of Child Health and Human Development (HD057773-01)
- Carey Farquhar
National Institute of Child Health and Human Development (HD054314)
- Carey Farquhar
Rosetreees Trust PhD Studentship (M876)
- Juanita Pang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Margaret Stanley, University of Cambridge, United Kingdom
Version history
- Received: September 17, 2020
- Accepted: December 31, 2020
- Accepted Manuscript published: December 31, 2020 (version 1)
- Version of Record published: January 13, 2021 (version 2)
Copyright
© 2020, Pang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Mixed cytomegalovirus genotypes in HIV positive mothers show compartmentalization and distinct patterns of transmission to infants
eLife 9:e63199.
https://doi.org/10.7554/eLife.63199
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