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


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.


Vyšlo v časopise: Extensive Genome-Wide Variability of Human Cytomegalovirus in Congenitally Infected Infants. PLoS Pathog 7(5): e32767. doi:10.1371/journal.ppat.1001344
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001344

Souhrn

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.


Zdroje

1. DowdJB

AielloAE

AlleyDE

2009 Socioeconomic disparities in the seroprevalence of cytomegalovirus infection in the US population: NHANES III. Epidemiol Infect 137 58 65

2. MurphJR

SouzaIE

DawsonJD

BensonP

PetheramSJ

1998 Epidemiology of Congenital Cytomegalovirus Infection: Maternal Risk Factors and Molecular Analysis of Cytomegalovirus Strains. Am J Epidemiol 147 940 947

3. ArvinAM

FastP

MyersM

PlotkinS

RabinovichR

2004 Vaccine development to prevent cytomegalovirus disease: report from the National Vaccine Advisory Committee. Clin Infect Dis 39 233 239

4. HassanJ

ConnellJ

2007 Translational Mini-Review Series on Infectious Disease:Congenital cytomegalovirus infection: 50 years on. Clin Exp Immunol 149 205 210

5. DolanA

CunninghamC

HectorRD

Hassan-WalkerAF

LeeL

2004 Genetic content of wild-type human cytomegalovirus. J Gen Virol 85 1301 1312

6. DavisonAJ

DolanA

AkterP

AddisonC

DarganDJ

2003 The human cytomegalovirus genome revisited: comparison with the chimpanzee cytomegalovirus genome. J Gen Virol 84 17 28

7. ChaTA

TomE

KembleGW

DukeGM

MocarskiES

1996 Human cytomegalovirus clinical isolates carry at least 19 genes not found in laboratory strains. J Virol 70 78 83

8. PrichardMN

PenfoldME

DukeGM

SpaeteRR

KembleGW

2001 A review of genetic differences between limited and extensively passaged human cytomegalovirus strains. Rev Med Virol 11 191 200

9. HeoJ

PetheramS

DemmlerG

MurphJR

AdlerSP

2008 Polymorphisms within human cytomegalovirus chemokine (UL146/UL147) and cytokine receptor genes (UL144) are not predictive of sequelae in congenitally infected children. Virology 378 86 96

10. JiYH

Rong SunZ

RuanQ

GuoJJ

HeR

2006 Polymorphisms of human cytomegalovirus UL148A, UL148B, UL148C, UL148D genes in clinical strains. J Clin Virol 37 252 257

11. HeR

RuanQ

QiY

MaYP

HuangYJ

2006 Sequence variability of human cytomegalovirus UL143 in low-passage clinical isolates. Chin Med J (Engl) 119 397 402

12. MaYP

RuanQ

HeR

QiY

SunZR

2006 Sequence variability of the human cytomegalovirus UL141 Open Reading Frame in clinical strains. Arch Virol 151 827 835

13. Arav-BogerR

BattagliaCA

LazzarottoT

GabrielliL

ZongJC

2006 Cytomegalovirus (CMV)-encoded UL144 (truncated tumor necrosis factor receptor) and outcome of congenital CMV infection. J Infect Dis 194 464 473

14. Arav-BogerR

FosterCB

ZongJC

PassRF

2006 Human cytomegalovirus-encoded alpha -chemokines exhibit high sequence variability in congenitally infected newborns. J Infect Dis 193 788 791

15. PignatelliS

Dal MonteP

RossiniG

LazzarottoT

GattoMR

2003 Intrauterine cytomegalovirus infection and glycoprotein N (gN) genotypes. J Clin Virol 28 38 43

16. BarM

Shannon-LoweC

GeballeAP

2001 Differentiation of Human Cytomegalovirus Genotypes in Immunocompromised Patients on the Basis of UL4 Gene Polymorphisms. J Infect Dis 183 218 225

17. SekulinK

GorzerI

Heiss-CzedikD

Puchhammer-StocklE

2007 Analysis of the variability of CMV strains in the RL11D domain of the RL11 multigene family. Virus Genes 35 577 583

18. RasmussenL

GeisslerA

CowanC

ChaseA

WintersM

2002 The Genes Encoding the gCIII Complex of Human Cytomegalovirus Exist in Highly Diverse Combinations in Clinical Isolates. J Virol 76 10841 10848

19. ChouS

1992 Comparative analysis of sequence variation in gp116 and gp55 components of glycoprotein B of human cytomegalovirus. Virology 188 388 390

20. PignatelliS

Dal MonteP

LandiniMP

2001 gpUL73 (gN) genomic variants of human cytomegalovirus isolates are clustered into four distinct genotypes. J Gen Virol 82 2777 2784

21. BenedictCA

ButrovichKD

LurainNS

CorbeilJ

RooneyI

1999 Cutting Edge: A Novel Viral TNF Receptor Superfamily Member in Virulent Strains of Human Cytomegalovirus. J Immunol 162 6967 6970

22. PenfoldME

DairaghiDJ

DukeGM

SaederupN

MocarskiES

1999 Cytomegalovirus encodes a potent alpha chemokine. Proc Natl Acad Sci U S A 96 9839 9844

23. YanH

KoyanoS

InamiY

YamamotoY

SuzutaniT

2008 Genetic variations in the gB, UL144 and UL149 genes of human cytomegalovirus strains collected from congenitally and postnatally infected Japanese children. Arch Virol 153 667 674

24. MurayamaT

TakegoshiM

TanumaJ

EizuruY

2005 Analysis of human cytomegalovirus UL144 variability in low-passage clinical isolates in Japan. Intervirology 48 201 206

25. BaleJFJr

PetheramSJ

RobertsonM

MurphJR

DemmlerG

2001 Human cytomegalovirus a sequence and UL144 variability in strains from infected children. J Med Virol 65 90 96

26. HumarA

KumarD

GilbertC

BoivinG

2003 Cytomegalovirus (CMV) Glycoprotein B Genotypes and Response to Antiviral Therapy, in Solid-Organ-Transplant Recipients with CMV Disease. J Infect Dis 188 581 584

27. CoaquetteA

BourgeoisA

DirandC

VarinA

ChenW

2004 Mixed Cytomegalovirus Glycoprotein B Genotypes in Immunocompromised Patients. Clin Infect Dis 39 155 161

28. PeekR

VerbraakF

BruinenbergM

Van der LelijA

Van den HornG

1998 Cytomegalovirus glycoprotein B genotyping in ocular fluids and blood of AIDS patients with cytomegalovirus retinitis. Invest Ophthalmol Vis Sci 39 1183 1187

29. PangX

HumarA

PreiksaitisJK

2008 Concurrent Genotyping and Quantitation of Cytomegalovirus gB Genotypes in Solid-Organ-Transplant Recipients by Use of a Real-Time PCR Assay. J Clin Microbiol 46 4004 4010

30. SarcinellaL

MazzulliT

WilleyB

HumarA

2002 Cytomegalovirus glycoprotein B genotype does not correlate with outcomes in liver transplant patients. J Clin Virol 24 99 105

31. BradleyAJ

KovácsIJ

GathererD

DarganDJ

AlkharsahKR

2008 Genotypic analysis of two hypervariable human cytomegalovirus genes. J Med Virol 80 1615 1623

32. StantonR

WestmorelandD

FoxJD

DavisonAJ

WilkinsonGW

2005 Stability of human cytomegalovirus genotypes in persistently infected renal transplant recipients. J Med Virol 75 42 46

33. GörzerI

KerschnerH

JakschP

BauerC

SeebacherG

2008 Virus load dynamics of individual CMV-genotypes in lung transplant recipients with mixed-genotype infections. J Med Virol 80 1405 1414

34. SowmyaP

MadhavanHN

2009 Analysis of mixed infections by multiple genotypes of human cytomegalovirus in immunocompromised patients. J Med Virol 81 861 869

35. Hassan-WalkerAF

OkwuadiS

LeeL

GriffithsPD

EmeryVC

2004 Sequence variability of the alpha-chemokine UL146 from clinical strains of human cytomegalovirus. J Med Virol 74 573 579

36. Puchhammer-StocklE

GorzerI

ZoufalyA

JakschP

BauerCC

2006 Emergence of multiple cytomegalovirus strains in blood and lung of lung transplant recipients. Transplantation 81 187 194

37. BradleyAJ

KovacsIJ

GathererD

DarganDJ

AlkharsahKR

2008 Genotypic analysis of two hypervariable human cytomegalovirus genes. J Med Virol 80 1615 1623

38. HolzerlandtR

OrengoC

KellamP

AlbaMM

2002 Identification of New Herpesvirus Gene Homologs in the Human Genome. Genome Res 12 1739 1748

39. PedenK

MountsP

HaywardGS

1982 Homology between mammalian cell DNA sequences and human herpesvirus genomes detected by a hybridization procedure with high-complexity probe. Cell 31 71 80

40. MurphyE

YuD

GrimwoodJ

SchmutzJ

DicksonM

2003 Coding potential of laboratory and clinical strains of human cytomegalovirus. Proc Natl Acad Sci U S A 100 14976 14981

41. SimmonsSL

DibartoloG

DenefVJ

GoltsmanDS

ThelenMP

2008 Population genomic analysis of strain variation in Leptospirillum group II bacteria involved in acid mine drainage formation. PLoS Biol 6 e177

42. TysonGW

ChapmanJ

HugenholtzP

AllenEE

RamRJ

2004 Community structure and metabolism through reconstruction of microbial genomes from the environment. Nature 428 37 43

43. MooreJH

2009 From genotypes to genometypes: putting the genome back in genome-wide association studies. Eur J Human Genet 17 1205 1206

44. GörzerI

GuellyC

TrajanoskiS

Puchhammer-StocklE

2010 Deep sequencing reveals highly complex dynamics of human cytomegalovirus genotypes in transplant patients over time. J VirolJ:VI 00475 00410

45. NeiM

LiWH

1979 Mathematical model for studying genetic variation in terms of restriction endonucleases. Proc Natl Acad Sci U S A 76 5269 5273

46. ZhuT

MoH

WangN

NamDS

CaoY

1993 Genotypic and phenotypic characterization of HIV-1 patients with primary infection. Science 261 1179 1181

47. Salazar-GonzalezJF

SalazarMG

KeeleBF

LearnGH

GiorgiEE

2009 Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection. J Exp Med 206 1273 1289

48. JerzakG

BernardKA

KramerLD

EbelGD

2005 Genetic variation in West Nile virus from naturally infected mosquitoes and birds suggests quasispecies structure and strong purifying selection. J Gen Virol 86 2175 2183

49. TroeschM

MeunierI

LapierreP

LapointeN

AlvarezF

2006 Study of a novel hypervariable region in hepatitis C virus (HCV) E2 envelope glycoprotein. Virology 352 357 367

50. WangWK

LinSR

LeeCM

KingCC

ChangSC

2002 Dengue type 3 virus in plasma is a population of closely related genomes: quasispecies. J Virol 76 4662 4665

51. HolmesEC

2003 Patterns of Intra- and Interhost Nonsynonymous Variation Reveal Strong Purifying Selection in Dengue Virus. J Virol 77 11296 11298

52. SylwesterAW

MitchellBL

EdgarJB

TaorminaC

PelteC

2005 Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects. J Exp Med 202 673 685

53. NishiyamaY

MaenoK

YoshidaS

1983 Characterization of human cytomegalovirus-induced DNA polymerase and the associated 3′-to-5′, exonuclease. Virology 124 221 231

54. NielsenR

WilliamsonS

KimY

HubiszMJ

ClarkAG

2005 Genomic scans for selective sweeps using SNP data. Genome Res 15 1566 1575

55. SmithJM

HaighJ

1974 The hitch-hiking effect of a favourable gene. Genet Res 23 23 35

56. KaplanNL

HudsonRR

LangleyCH

1989 The "hitchhiking effect" revisited. Genetics 123 887 899

57. Arav-BogerR

ZongJC

FosterCB

2005 Loss of linkage disequilibrium and accelerated protein divergence in duplicated cytomegalovirus chemokine genes. Virus Genes 31 65 72

58. YanH

KoyanoS

InamiY

YamamotoY

SuzutaniT

2008 Genetic linkage among human cytomegalovirus glycoprotein N (gN) and gO genes, with evidence for recombination from congenitally and post-natally infected Japanese infants. J Gen Virol 89 2275 2279

59. McDonaldJH

KreitmanM

1991 Adaptive protein evolution at the Adh locus in Drosophila. Nature 351 652 654

60. GibsonL

PiccininiG

LilleriD

RevelloMG

WangZ

2004 Human cytomegalovirus proteins pp65 and immediate early protein 1 are common targets for CD8+ T cell responses in children with congenital or postnatal human cytomegalovirus infection. J Immunol 172 2256 2264

61. CunninghamC

GathererD

HilfrichB

BaluchovaK

DarganDJ

2009 Sequences of complete human cytomegalovirus genomes from infected cell cultures and clinical specimens. J Gen Virol 91 605 615

62. SpatzSJ

2010 Accumulation of attenuating mutations in varying proportions within a high passage very virulent plus strain of Gallid herpesvirus type 2. Virus Res 149 135 142

63. YuD

SmithGA

EnquistLW

ShenkT

2002 Construction of a self-excisable bacterial artificial chromosome containing the human cytomegalovirus genome and mutagenesis of the diploid TRL/IRL13 gene. J Virol 76 2316 2328

64. GaultE

MichelY

DeheeA

BelabaniC

NicolasJC

2001 Quantification of human cytomegalovirus DNA by real-time PCR. J Clin Microbiol 39 772 775

65. QuailMA

KozarewaI

SmithF

ScallyA

StephensPJ

2008 A large genome center's improvements to the Illumina sequencing system. Nat Methods 5 1005 1010

66. LiH

RuanJ

DurbinR

2008 Mapping short DNA sequencing reads and calling variants using mapping quality scores. Genome Res 18 1851 1858

67. BentleyDR

BalasubramanianS

SwerdlowHP

SmithGP

MiltonJ

2008 Accurate whole human genome sequencing using reversible terminator chemistry. Nature 456 53 59

68. DohmJC

LottazC

BorodinaT

HimmelbauerH

2007 SHARCGS, a fast and highly accurate short-read assembly algorithm for de novo genomic sequencing. Genome Res 17 1697 1706

69. DrummondAJ

AshtonB

BuxtonS

CheungM

HeledJ

2010 Geneious, version 4.8. Biomatters, Inc Available: http://www.geneious.com

70. HudsonRR

2002 Generating samples under a Wright-Fisher neutral model of genetic variation. Bioinformatics 18 337 338

71. LibradoP

RozasJ

2009 DnaSP v5: a software for comprehensive analysis of DNA polymorphism data. Bioinformatics 25 1451 1452

72. EgeaR

CasillasS

BarbadillaA

2008 Standard and generalized McDonald-Kreitman test: a website to detect selection by comparing different classes of DNA sites. Nucleic Acids Res 36 W157 162

73. NeiM

GojoboriT

1986 Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol 3 418 426

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