Characterizing human cytomegalovirus reinfection in congenitally infected infants: an evolutionary perspective

Cornelia Pokalyuk, Nicholas Renzette, Kristen K. Irwin, Susanne Pfeifer, Laura Gibson, William J. Britt, Aparecida Y. Yamamoto, Marisa M. Mussi-Pinhata, Timothy F. Kowalik, Jeffrey Jensen

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Given the strong selective pressures often faced by populations when colonizing a novel habitat, the level of variation present on which selection may act is an important indicator of adaptive potential. While often discussed in an ecological context, this notion is also highly relevant in our clinical understanding of viral infection, in which the novel habitat is a new host. Thus, quantifying the factors determining levels of variation is of considerable importance for the design of improved treatment strategies. Here, we focus on such a quantification of human cytomegalovirus (HCMV) – a virus which can be transmitted across the placenta, resulting in foetal infection that can potentially cause severe disease in multiple organs. Recent studies using genomewide sequencing data have demonstrated that viral populations in some congenitally infected infants diverge rapidly over time and between tissue compartments within individuals, while in other infants, the populations remain highly stable. Here, we investigate the underlying causes of these extreme differences in observed intrahost levels of variation by estimating the underlying demographic histories of infection. Importantly, reinfection (i.e. population admixture) appears to be an important, and previously unappreciated, player. We highlight illustrative examples likely to represent a single-population transmission from a mother during pregnancy and multiple-population transmissions during pregnancy and after birth.

Original languageEnglish (US)
Pages (from-to)1980-1990
Number of pages11
JournalMolecular ecology
Volume26
Issue number7
DOIs
StatePublished - Apr 2017

Keywords

  • evolutionary medicine
  • molecular evolution
  • population genetics – empirical

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics

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