Department of Microbiology and Physiological Systems; Department of Pediatrics; Department of Medicine, Division of Infectious Diseases and Immunology
Cluster Analysis; Cytomegalovirus; Cytomegalovirus Infections; Evolution, Molecular; Gene Expression Regulation; Genes, Viral; *Genetic Variation; *Genome, Viral; Genomics; Glycoproteins; Humans; Infant; Infant, Newborn; Mutation; Polymorphism, Genetic; Recombination, Genetic; Sequence Analysis, DNA
Genetics | Genomics | Immunology of Infectious Disease | Microbiology | Population Biology
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 approximately 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.
HCMV, congenital CMV, evolution, human cytomegalovirus, virology, UMCCTS funding
Rights and Permissions
Freely available online through the PNAS open access option.
DOI of Published Version
Proc Natl Acad Sci U S A. 2015 Jul 28;112(30):E4120-8. doi: 10.1073/pnas.1501880112. Epub 2015 Jul 6. Link to article on publisher's site
Proceedings of the National Academy of Sciences of the United States of America
Renzette, Nicholas; Pokalyuk, Cornelia; Gibson, Laura; Bhattacharjee, Bornali; Schleiss, Mark R.; Hamprecht, Klaus; Yamamoto, Aparecida Y.; Mussi-Pinhata, Marisa M.; Britt, William J.; Jensen, Jeffrey D.; and Kowalik, Timothy F., "Limits and patterns of cytomegalovirus genomic diversity in humans" (2015). Open Access Articles. 2690.