title: Characterizing human cytomegalovirus reinfection in congenitally infected infants: an evolutionary perspective.
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.
authors.affiliation: Institute for Mathematics, Goethe Universität Frankfurt, Frankfurt am Main, Germany.|Faculty for Mathematics, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.|School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.|Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Pokalyuk
authors.affiliation: Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.|Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Renzette
authors.affiliation: School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.|Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
authors.forename: Kristen K
authors.initials: KK
authors.lastname: Irwin
authors.affiliation: School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.|Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.|School of Life Sciences, Arizona State University, Tempe, AZ, USA.
authors.forename: Susanne P
authors.initials: SP
authors.lastname: Pfeifer
authors.affiliation: Departments of Medicine and Pediatrics, Divisions of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Gibson
authors.affiliation: Department of Pediatrics, University of Alabama Birmingham, School of Medicine, Birmingham, AL, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Britt
authors.affiliation: Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Aparecida Y
authors.initials: AY
authors.lastname: Yamamoto
authors.affiliation: Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Marisa M
authors.initials: MM
authors.lastname: Mussi-Pinhata
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Kowalik
authors.affiliation: School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.|Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.|School of Life Sciences, Arizona State University, Tempe, AZ, USA.
authors.forename: Jeffrey D
authors.identifier: http://orcid.org/0000-0002-4786-8064
authors.initials: JD
authors.lastname: Jensen
mesh_terms: D003587:Cytomegalovirus / Q000235:genetics*; D003586:Cytomegalovirus Infections / Q000151:congenital* / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D014644:Genetic Variation; D005828:Genetics, Population; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008957:Models, Genetic; D011247:Pregnancy; D017422:Sequence Analysis, DNA
chemical_list: D004279:DNA, Viral
keywords: evolutionary medicine; molecular evolution; population genetics - empirical