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.
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.
Metrics
-
- 1,123
- views
-
- 165
- downloads
-
- 19
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
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
Further reading
-
- Genetics and Genomics
Advances in single-cell sequencing technologies have provided novel insights into the dynamics of gene expression and cellular heterogeneity within tissues and have enabled the construction of transcriptomic cell atlases. However, linking anatomical information to transcriptomic data and positively identifying the cell types that correspond to gene expression clusters in single-cell sequencing data sets remains a challenge. We describe a straightforward genetic barcoding approach that takes advantage of the powerful genetic tools in Drosophila to allow in vivo tagging of defined cell populations. This method, called Targeted Genetically-Encoded Multiplexing (TaG-EM), involves inserting a DNA barcode just upstream of the polyadenylation site in a Gal4-inducible UAS-GFP construct so that the barcode sequence can be read out during single-cell sequencing, labeling a cell population of interest. By creating many such independently barcoded fly strains, TaG-EM enables positive identification of cell types in cell atlas projects, identification of multiplet droplets, and barcoding of experimental timepoints, conditions, and replicates. Furthermore, we demonstrate that TaG-EM barcodes can be read out using next-generation sequencing to facilitate population-scale behavioral measurements. Thus, TaG-EM has the potential to enable large-scale behavioral screens in addition to improving the ability to multiplex and reliably annotate single-cell transcriptomic experiments.
-
- Genetics and Genomics
RNAs in circulation carry sequence-specific regulatory information between cells in plant, animal, and host-pathogen systems. Such RNA can cross generational boundaries, as evidenced by somatic double-stranded RNA (dsRNA) in the nematode Caenorhabditis elegans silencing genes of matching sequence in progeny. Here we dissect the intergenerational path taken by dsRNA from parental circulation and discover that cytosolic import through the dsRNA importer SID-1 in the parental germline and/or developing progeny varies with developmental time and dsRNA substrates. Loss of SID-1 enhances initiation of heritable RNA silencing within the germline and causes changes in the expression of the sid-1-dependent gene sdg-1 that last for more than 100 generations after restoration of SID-1. The SDG-1 protein is enriched in perinuclear germ granules required for heritable RNA silencing but is expressed from a retrotransposon targeted by such silencing. This auto-inhibitory loop suggests how retrotransposons could persist by hosting genes that regulate their own silencing.
