Limits and patterns of cytomegalovirus genomic diversity in humans
Authors
Renzette, NicholasPokalyuk, Cornelia
Gibson, Laura
Bhattacharjee, Bornali
Schleiss, Mark R.
Hamprecht, Klaus
Yamamoto, Aparecida Y.
Mussi-Pinhata, Marisa M.
Britt, William J.
Jensen, Jeffrey D.
Kowalik, Timothy F.
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDepartment of Pediatrics
Department of Microbiology and Physiological Systems
Document Type
Journal ArticlePublication Date
2015-07-28Keywords
Cluster AnalysisCytomegalovirus
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
HCMV
congenital CMV
evolution
human cytomegalovirus
virology
UMCCTS funding
Genetics
Genomics
Immunology of Infectious Disease
Microbiology
Population Biology
Metadata
Show full item recordAbstract
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.Source
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
DOI
10.1073/pnas.1501880112Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39889PubMed ID
26150505Related Resources
Rights
Freely available online through the PNAS open access option.
ae974a485f413a2113503eed53cd6c53
10.1073/pnas.1501880112