title: Limits and patterns of cytomegalovirus genomic diversity in humans.
abstract: Human cytomegalovirus (HCMV) exhibits surprisingly high genomic diversity during natural infection although little is known about the limits or patterns of HCMV diversity among humans. To address this deficiency, we analyzed genomic diversity among congenitally infected infants. We show that there is an upper limit to HCMV genomic diversity in these patient samples, with ∼ 25% of the genome being devoid of polymorphisms. These low diversity regions were distributed across 26 loci that were preferentially located in DNA-processing genes. Furthermore, by developing, to our knowledge, the first genome-wide mutation and recombination rate maps for HCMV, we show that genomic diversity is positively correlated with these two rates. In contrast, median levels of viral genomic diversity did not vary between putatively single or mixed strain infections. We also provide evidence that HCMV populations isolated from vascular compartments of hosts from different continents are genetically similar and that polymorphisms in glycoproteins and regulatory proteins are enriched in these viral populations. This analysis provides the most highly detailed map of HCMV genomic diversity in human hosts to date and informs our understanding of the distribution of HCMV genomic diversity within human hosts.
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655;
authors.forename: Nicholas
authors.initials: N
authors.lastname: Renzette
authors.affiliation: Institute for Stochastics, Goethe Universität Frankfurt, D-60325 Frankfurt am Main, Germany; Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland;
authors.forename: Cornelia
authors.initials: C
authors.lastname: Pokalyuk
authors.affiliation: Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA 01605; Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655;
authors.forename: Laura
authors.initials: L
authors.lastname: Gibson
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655;
authors.forename: Bornali
authors.initials: B
authors.lastname: Bhattacharjee
authors.affiliation: Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota Medical School, Minneapolis, MN 55455; Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55455;
authors.forename: Mark R
authors.initials: MR
authors.lastname: Schleiss
authors.affiliation: Institute for Medical Virology, University Hospital Tübingen, 72076 Tübingen, Germany;
authors.forename: Klaus
authors.initials: K
authors.lastname: Hamprecht
authors.affiliation: Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto-São Paulo 14048-900, Brazil;
authors.forename: Aparecida Y
authors.initials: AY
authors.lastname: Yamamoto
authors.affiliation: Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto-São Paulo 14048-900, Brazil;
authors.forename: Marisa M
authors.initials: MM
authors.lastname: Mussi-Pinhata
authors.affiliation: Department of Pediatrics, University of Alabama Birmingham School of Medicine, Birmingham, AL 35294;
authors.forename: William J
authors.initials: WJ
authors.lastname: Britt
authors.affiliation: Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland; School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland; Timothy.Kowalik@umassmed.edu jeffrey.jensen@epfl.ch.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Jensen
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655; Immunology and Virology Program, University of Massachusetts Medical School, Worcester, MA 01655 Timothy.Kowalik@umassmed.edu jeffrey.jensen@epfl.ch.
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Kowalik
mesh_terms: D016000:Cluster Analysis; D003587:Cytomegalovirus / Q000235:genetics* / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000821:virology*; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D005814:Genes, Viral; D014644:Genetic Variation; D016679:Genome, Viral; D023281:Genomics; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009154:Mutation; D011110:Polymorphism, Genetic; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D006023:Glycoproteins
keywords: HCMV; congenital CMV; evolution; human cytomegalovirus; virology