1. Genetics and Genomics
  2. Microbiology and Infectious Disease
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Mixed cytomegalovirus genotypes in HIV positive mothers show compartmentalization and distinct patterns of transmission to infants

  1. Juanita Pang
  2. Jennifer A Slyker
  3. Sunando Roy
  4. Josephine Bryant
  5. Claire Atkinson
  6. Juliana Cudini
  7. Carey Farquhar
  8. Paul Griffiths
  9. James Kiarie
  10. Sofia Morfopoulou
  11. Alison C Roxby
  12. Helena Tutil
  13. Rachel Williams
  14. Soren Gantt
  15. Richard A Goldstein
  16. Judith Breuer  Is a corresponding author
  1. University College London, United Kingdom
  2. University of Washington, United States
  3. University College of London, United Kingdom
  4. University of Nairobi, Kenya
  5. University of Montréal, Canada
Research Article
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Cite this article as: eLife 2020;9:e63199 doi: 10.7554/eLife.63199

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

  1. Juanita Pang

    Division of Infection and Immunity, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Jennifer A Slyker

    Department of Global Health, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Sunando Roy

    Division of Infection and Immunity, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Josephine Bryant

    Division of Infection and Immunity, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Claire Atkinson

    Division of Infection and Immunity, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Juliana Cudini

    Division of Infection and Immunity, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Carey Farquhar

    Departments of Global Health, Epidemiology, Medicine (Div. Allergy and Infectious Diseases), University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Paul Griffiths

    University College of London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. James Kiarie

    Department of Obstetrics and Gynaecology, University of Nairobi, Nairobi, Kenya
    Competing interests
    The authors declare that no competing interests exist.
  10. Sofia Morfopoulou

    Division of Infection and Immunity, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. Alison C Roxby

    Department of Global Health, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Helena Tutil

    Division of Infection and Immunity, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  13. Rachel Williams

    Division of Infection and Immunity, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  14. Soren Gantt

    Infectious Diseases and Immunology, University of Montréal, Montréal, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5743-3606
  15. Richard A Goldstein

    Division of Infection and Immunity, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5148-4672
  16. Judith Breuer

    Division of Infection and Immunity, University College London, London, United Kingdom
    For correspondence
    j.breuer@ucl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8246-0534

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

  1. Margaret Stanley, University of Cambridge, United Kingdom

Publication history

  1. Received: September 17, 2020
  2. Accepted: December 31, 2020
  3. Accepted Manuscript published: December 31, 2020 (version 1)
  4. 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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