Limits and patterns of cytomegalovirus genomic diversity in humans

Nicholas Renzette, Cornelia Pokalyuk, Laura Gibson, Bornali Bhattacharjee, Mark R. Schleiss, Klaus Hamprecht, Aparecida Y. Yamamoto, Marisa M. Mussi-Pinhata, William J. Britt, Jeffrey D. Jensen, Timothy F. Kowalik

Research output: Contribution to journalArticle

60 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)E4120-E4128
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number30
DOIs
StatePublished - Jul 28 2015

Keywords

  • Congenital CMV
  • Evolution
  • HCMV
  • Human cytomegalovirus
  • Virology

ASJC Scopus subject areas

  • General

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  • Cite this

    Renzette, N., Pokalyuk, C., Gibson, L., Bhattacharjee, B., Schleiss, M. R., Hamprecht, K., Yamamoto, A. Y., Mussi-Pinhata, M. M., Britt, W. J., Jensen, J. D., & Kowalik, T. F. (2015). Limits and patterns of cytomegalovirus genomic diversity in humans. Proceedings of the National Academy of Sciences of the United States of America, 112(30), E4120-E4128. https://doi.org/10.1073/pnas.1501880112