Extensive Genome-wide Variability of Human Cytomegalovirus in Congenitally Infected Infants

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2011 Jun 1

PMID 21625576

Citations 132

Authors

Nicholas Renzette

Bornali Bhattacharjee

Jeffrey D Jensen

Laura Gibson

Timothy F Kowalik

Affiliations

Soon will be listed here.

Abstract

Research has shown that RNA virus populations are highly variable, most likely due to low fidelity replication of RNA genomes. It is generally assumed that populations of DNA viruses will be less complex and show reduced variability when compared to RNA viruses. Here, we describe the use of high throughput sequencing for a genome wide study of viral populations from urine samples of neonates with congenital human cytomegalovirus (HCMV) infections. We show that HCMV intrahost genomic variability, both at the nucleotide and amino acid level, is comparable to many RNA viruses, including HIV. Within intrahost populations, we find evidence of selective sweeps that may have resulted from immune-mediated mechanisms. Similarly, genome wide, population genetic analyses suggest that positive selection has contributed to the divergence of the HCMV species from its most recent ancestor. These data provide evidence that HCMV, a virus with a large dsDNA genome, exists as a complex mixture of genome types in humans and offer insights into the evolution of the virus.

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References

Nei M, Li W . Mathematical model for studying genetic variation in terms of restriction endonucleases. Proc Natl Acad Sci U S A. 1979; 76(10):5269-73. PMC: 413122. DOI: 10.1073/pnas.76.10.5269. View

Librado P, Rozas J . DnaSP v5: a software for comprehensive analysis of DNA polymorphism data. Bioinformatics. 2009; 25(11):1451-2. DOI: 10.1093/bioinformatics/btp187. View

Gorzer I, Guelly C, Trajanoski S, Puchhammer-Stockl E . Deep sequencing reveals highly complex dynamics of human cytomegalovirus genotypes in transplant patients over time. J Virol. 2010; 84(14):7195-203. PMC: 2898262. DOI: 10.1128/JVI.00475-10. View

Coaquette A, Bourgeois A, Dirand C, Varin A, Chen W, Herbein G . Mixed cytomegalovirus glycoprotein B genotypes in immunocompromised patients. Clin Infect Dis. 2004; 39(2):155-61. DOI: 10.1086/421496. View

Moore J . From genotypes to genometypes: putting the genome back in genome-wide association studies. Eur J Hum Genet. 2009; 17(10):1205-6. PMC: 2986649. DOI: 10.1038/ejhg.2009.39. View

Prichard M, Penfold M, Duke G, Spaete R, Kemble G . A review of genetic differences between limited and extensively passaged human cytomegalovirus strains. Rev Med Virol. 2001; 11(3):191-200. DOI: 10.1002/rmv.315. View

Davison A, Dolan A, Akter P, Addison C, Dargan D, Alcendor D . The human cytomegalovirus genome revisited: comparison with the chimpanzee cytomegalovirus genome. J Gen Virol. 2003; 84(Pt 1):17-28. DOI: 10.1099/vir.0.18606-0. View

Holzerlandt R, Orengo C, Kellam P, Alba M . Identification of new herpesvirus gene homologs in the human genome. Genome Res. 2002; 12(11):1739-48. PMC: 187546. DOI: 10.1101/gr.334302. View

Peden K, Mounts P, Hayward G . Homology between mammalian cell DNA sequences and human herpesvirus genomes detected by a hybridization procedure with high-complexity probe. Cell. 1982; 31(1):71-80. DOI: 10.1016/0092-8674(82)90406-8. View

10.

He R, Ruan Q, Qi Y, Ma Y, Huang Y, Sun Z . Sequence variability of human cytomegalovirus UL143 in low-passage clinical isolates. Chin Med J (Engl). 2006; 119(5):397-402. View

11.

Dohm J, Lottaz C, Borodina T, Himmelbauer H . SHARCGS, a fast and highly accurate short-read assembly algorithm for de novo genomic sequencing. Genome Res. 2007; 17(11):1697-706. PMC: 2045152. DOI: 10.1101/gr.6435207. View

12.

Murph J, Souza I, Dawson J, Benson P, Petheram S, Pfab D . Epidemiology of congenital cytomegalovirus infection: maternal risk factors and molecular analysis of cytomegalovirus strains. Am J Epidemiol. 1998; 147(10):940-7. DOI: 10.1093/oxfordjournals.aje.a009384. View

13.

Pang X, Humar A, Preiksaitis J . Concurrent genotyping and quantitation of cytomegalovirus gB genotypes in solid-organ-transplant recipients by use of a real-time PCR assay. J Clin Microbiol. 2008; 46(12):4004-10. PMC: 2593284. DOI: 10.1128/JCM.01341-08. View

14.

Heo J, Petheram S, Demmler G, Murph J, Adler S, Bale J . Polymorphisms within human cytomegalovirus chemokine (UL146/UL147) and cytokine receptor genes (UL144) are not predictive of sequelae in congenitally infected children. Virology. 2008; 378(1):86-96. PMC: 2585519. DOI: 10.1016/j.virol.2008.05.002. View

15.

Rasmussen L, Geissler A, Cowan C, Chase A, Winters M . The genes encoding the gCIII complex of human cytomegalovirus exist in highly diverse combinations in clinical isolates. J Virol. 2002; 76(21):10841-8. PMC: 136653. DOI: 10.1128/jvi.76.21.10841-10848.2002. View

16.

McDonald J, Kreitman M . Adaptive protein evolution at the Adh locus in Drosophila. Nature. 1991; 351(6328):652-4. DOI: 10.1038/351652a0. View

17.

Ji Y, Sun Z, Ruan Q, Guo J, He R, Qi Y . Polymorphisms of human cytomegalovirus UL148A, UL148B, UL148C, UL148D genes in clinical strains. J Clin Virol. 2006; 37(4):252-7. DOI: 10.1016/j.jcv.2006.09.007. View

18.

Egea R, Casillas S, Barbadilla A . Standard and generalized McDonald-Kreitman test: a website to detect selection by comparing different classes of DNA sites. Nucleic Acids Res. 2008; 36(Web Server issue):W157-62. PMC: 2447769. DOI: 10.1093/nar/gkn337. View

19.

Arav-Boger R, Foster C, Zong J, Pass R . Human cytomegalovirus-encoded alpha -chemokines exhibit high sequence variability in congenitally infected newborns. J Infect Dis. 2006; 193(6):788-91. DOI: 10.1086/500508. View

20.

Nielsen R, Williamson S, Kim Y, Hubisz M, Clark A, Bustamante C . Genomic scans for selective sweeps using SNP data. Genome Res. 2005; 15(11):1566-75. PMC: 1310644. DOI: 10.1101/gr.4252305. View