Rapid Intrahost Evolution of Human Cytomegalovirus Is Shaped by Demography and Positive Selection

Nicholas Renzette, Laura Gibson, Bornali Bhattacharjee, Donna Fisher, Mark R. Schleiss, Jeffrey Jensen, Timothy F. Kowalik

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Populations of human cytomegalovirus (HCMV), a large DNA virus, are highly polymorphic in patient samples, which may allow for rapid evolution within human hosts. To understand HCMV evolution, longitudinally sampled genomic populations from the urine and plasma of 5 infants with symptomatic congenital HCMV infection were analyzed. Temporal and compartmental variability of viral populations were quantified using high throughput sequencing and population genetics approaches. HCMV populations were generally stable over time, with ∼88% of SNPs displaying similar frequencies. However, samples collected from plasma and urine of the same patient at the same time were highly differentiated with approximately 1700 consensus sequence SNPs (1.2% of the genome) identified between compartments. This inter-compartment differentiation was comparable to the differentiation observed in unrelated hosts. Models of demography (i.e., changes in population size and structure) and positive selection were evaluated to explain the observed patterns of variation. Evidence for strong bottlenecks (>90% reduction in viral population size) was consistent among all patients. From the timing of the bottlenecks, we conclude that fetal infection occurred between 13-18 weeks gestational age in patients analyzed, while colonization of the urine compartment followed roughly 2 months later. The timing of these bottlenecks is consistent with the clinical histories of congenital HCMV infections. We next inferred that positive selection plays a small but measurable role in viral evolution within a single compartment. However, positive selection appears to be a strong and pervasive driver of evolution associated with compartmentalization, affecting ≥34 of the 167 open reading frames (∼20%) of the genome. This work offers the most detailed map of HCMV in vivo evolution to date and provides evidence that viral populations can be stable or rapidly differentiate, depending on host environment. The application of population genetic methods to these data provides clinically useful information, such as the timing of infection and compartment colonization.

Original languageEnglish (US)
Article numbere1003735
JournalPLoS Genetics
Volume9
Issue number9
DOIs
StatePublished - Sep 2013
Externally publishedYes

Fingerprint

Human herpesvirus 5
Cytomegalovirus
demography
Demography
urine
human evolution
population genetics
population size
colonization
genome
plasma
Cytomegalovirus Infections
Population Genetics
Urine
compartmentalization
Population Density
Population
Single Nucleotide Polymorphism
population structure
DNA viruses

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Renzette, N., Gibson, L., Bhattacharjee, B., Fisher, D., Schleiss, M. R., Jensen, J., & Kowalik, T. F. (2013). Rapid Intrahost Evolution of Human Cytomegalovirus Is Shaped by Demography and Positive Selection. PLoS Genetics, 9(9), [e1003735]. https://doi.org/10.1371/journal.pgen.1003735

Rapid Intrahost Evolution of Human Cytomegalovirus Is Shaped by Demography and Positive Selection. / Renzette, Nicholas; Gibson, Laura; Bhattacharjee, Bornali; Fisher, Donna; Schleiss, Mark R.; Jensen, Jeffrey; Kowalik, Timothy F.

In: PLoS Genetics, Vol. 9, No. 9, e1003735, 09.2013.

Research output: Contribution to journalArticle

Renzette, N, Gibson, L, Bhattacharjee, B, Fisher, D, Schleiss, MR, Jensen, J & Kowalik, TF 2013, 'Rapid Intrahost Evolution of Human Cytomegalovirus Is Shaped by Demography and Positive Selection', PLoS Genetics, vol. 9, no. 9, e1003735. https://doi.org/10.1371/journal.pgen.1003735
Renzette, Nicholas ; Gibson, Laura ; Bhattacharjee, Bornali ; Fisher, Donna ; Schleiss, Mark R. ; Jensen, Jeffrey ; Kowalik, Timothy F. / Rapid Intrahost Evolution of Human Cytomegalovirus Is Shaped by Demography and Positive Selection. In: PLoS Genetics. 2013 ; Vol. 9, No. 9.
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