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Proc Natl Acad Sci U S A. 2015 Jul 28;112(30):E4120-8. doi: 10.1073/pnas.1501880112. Epub 2015 Jul 6.

Limits and patterns of cytomegalovirus genomic diversity in humans.

Author information

1
Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655;
2
Institute for Stochastics, Goethe Universität Frankfurt, D-60325 Frankfurt am Main, Germany; Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland;
3
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;
4
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;
5
Institute for Medical Virology, University Hospital Tübingen, 72076 Tübingen, Germany;
6
Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto-São Paulo 14048-900, Brazil;
7
Department of Pediatrics, University of Alabama Birmingham School of Medicine, Birmingham, AL 35294;
8
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.
9
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.

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.

KEYWORDS:

HCMV; congenital CMV; evolution; human cytomegalovirus; virology

PMID:
26150505
PMCID:
PMC4522815
DOI:
10.1073/pnas.1501880112
[Indexed for MEDLINE]
Free PMC Article

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