Phylogenetic Approach Reveals That Virus Genotype Largely Determines HIV Set-Point Viral Load

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HIV virulence, i.e. the time of progression to AIDS, varies greatly among patients. As for other rapidly evolving pathogens of humans, it is difficult to know if this variance is controlled by the genotype of the host or that of the virus because the transmission chain is usually unknown. We apply the phylogenetic comparative approach (PCA) to estimate the heritability of a trait from one infection to the next, which indicates the control of the virus genotype over this trait. The idea is to use viral RNA sequences obtained from patients infected by HIV-1 subtype B to build a phylogeny, which approximately reflects the transmission chain. Heritability is measured statistically as the propensity for patients close in the phylogeny to exhibit similar infection trait values. The approach reveals that up to half of the variance in set-point viral load, a trait associated with virulence, can be heritable. Our estimate is significant and robust to noise in the phylogeny. We also check for the consistency of our approach by showing that a trait related to drug resistance is almost entirely heritable. Finally, we show the importance of taking into account the transmission chain when estimating correlations between infection traits. The fact that HIV virulence is, at least partially, heritable from one infection to the next has clinical and epidemiological implications. The difference between earlier studies and ours comes from the quality of our dataset and from the power of the PCA, which can be applied to large datasets and accounts for within-host evolution. The PCA opens new perspectives for approaches linking clinical data and evolutionary biology because it can be extended to study other traits or other infectious diseases.

Vyšlo v časopise: Phylogenetic Approach Reveals That Virus Genotype Largely Determines HIV Set-Point Viral Load. PLoS Pathog 6(9): e32767. doi:10.1371/journal.ppat.1001123
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001123

Souhrn

Zdroje

1. BuchbinderSP

KatzMH

HessolNA

O'MalleyPM

HolmbergSD

1994 Long-term HIV-1 infection without immunologic progression. AIDS 8 1123 8

2. FellayJ

ShiannaKV

GeD

ColomboS

LedergerberB

2007 A whole-genome association study of major determinants for host control of HIV-1. Science 317 944 947

3. FellayJ

GeD

ShiannaKV

ColomboS

LedergerberB

2009 Common genetic variation and the control of HIV-1 in humans. PLoS Genet 5 e1000791

4. WardJW

BushTJ

PerkinsHA

LiebLE

AllenJR

1989 The natural history of transfusion-associated infection with human immunodeficiency virus. Factors influencing the rate of progression to disease. N Engl J Med 321 947 52

5. AshtonLJ

LearmontJ

LuoK

WylieB

StewartG

1994 HIV infection in recipients of blood products from donors with known duration of infection. Lancet 344 718 20

6. IoannidisJPA

TatsioniA

AbramsEJ

BulterysM

CoombsRW

2004 Maternal viral load and rate of disease progression among vertically HIV-1-infected children: an international meta-analysis. AIDS 18 99 108

7. LynchM

WalshB

1998 Genetics and Analysis of Quantitative Traits Sunderland, MA, USA Sinauer Associates, Inc

8. HollingsworthTD

LaeyendeckerO

ShirreffG

DonnellyCA

SerwaddaD

2010 HIV-1 transmitting couples have similar viral load set-points in Rakai, Uganda. PLoS Pathog 6 e1000876

9. TangJ

TangS

LobashevskyE

ZuluI

AldrovandiG

2004 HLA allele sharing and HIV type 1 viremia in seroconverting Zambians with known transmitting partners. AIDS Res Hum Retroviruses 20 19 25

10. van der KuylAC

JurriaansS

PollakisG

BakkerM

CornelissenM

2010 HIV RNA levels in transmission sources only weakly predict plasma viral load in recipients. AIDS 24 1607 8

11. HechtFM

HartogensisW

BraggL

BacchettiP

AtchisonR

2010 HIV RNA level in early infection is predicted by viral load in the transmission source. AIDS 24 941 5

12. BlombergSP

GarlandTJ

IvesAR

2003 Testing for phylogenetic signal in comparative data: behavioral traits are more labile. Evolution 57 717 745

13. HousworthEA

MartinsEP

LynchM

2004 The phylogenetic mixed model. Am Nat 163 84 96

14. FelsensteinJ

2004 Inferring phylogenies Sunderland, MA, USA Sinauer Associates, Inc

15. The Swiss HIV Cohort Study 2010 Cohort Profile: The Swiss HIV Cohort Study. Int J Epidemiol in press doi:10.1093/ije/dyp321

16. FraserC

HollingsworthTD

ChapmanR

de WolfF

HanageWP

2007 Variation in HIV-1 set-point viral load: epidemiological analysis and an evolutionary hypothesis. Proc Natl Acad Sci USA 104 17441 17446

17. MüllerV

MaggioloF

SuterF

LadisaN

De LucaA

2009 Increasing clinical virulence in two decades of the Italian HIV epidemic. PLoS Pathog 5 e1000454

18. MellorsJW

RinaldoCRJ

GuptaP

WhiteRM

ToddJA

1996 Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science 272 1167 1170

19. LangfordSE

AnanworanichJ

CooperDA

2007 Predictors of disease progression in HIV infection: a review. AIDS Res Ther 4 11

20. MellorsJW

MargolickJB

PhairJP

RinaldoCR

DetelsR

2007 Prognostic value of HIV-1 RNA, CD4 cell count, and CD4 Cell count slope for progression to AIDS and death in untreated HIV-1 infection. JAMA 297 2349 50

21. MellorsJW

MuñozA

GiorgiJV

MargolickJB

TassoniCJ

1997 Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med 126 946 54

22. LeitnerT

EscanillaD

FranzenC

UhlenM

AlbertJ

1996 Accurate reconstruction of a known HIV-1 transmission history by phylogenetic tree analysis. Proc Natl Acad Sci USA 93 10864 10869

23. HuéS

ClewleyJP

CanePA

PillayD

2004 HIV-1 pol gene variation is sufficient for reconstruction of transmissions in the era of antiretroviral therapy. AIDS 18 719 728

24. FelsensteinJ

1985 Phylogenies and the Comparative Method. Am Nat 125 1 15

25. KouyosRD

von WylV

YerlyS

BöniJ

TafféP

2010 Molecular epidemiology reveals long-term changes in HIV type 1 subtype B transmission in Switzerland. J Infect Dis 201 1488 97

26. FreckletonRP

HarveyPH

PagelM

2002 Phylogenetic analysis and comparative data: a test and review of evidence. Am Nat 160 712 726

27. FreckletonRP

2009 The seven deadly sins of comparative analysis. J Evol Biol 22 1367 75

28. RodríguezB

SethiAK

CheruvuVK

MackayW

BoschRJ

2006 Predictive value of plasma HIV RNA level on rate of CD4 T-cell decline in untreated HIV infection. JAMA 296 1498 1506

29. KankiPJ

HamelDJ

SankaléJL

HsiehCc

ThiorI

1999 Human immunodeficiency virus type 1 subtypes differ in disease progression. J Infect Dis 179 68 73

30. AriënKK

VanhamG

ArtsEJ

2007 Is HIV-1 evolving to a less virulent form in humans? Nat Rev Microbiol 5 141 151

31. TaylorBS

SobieszczykME

McCutchanFE

HammerSM

2008 The challenge of HIV-1 subtype diversity. N Engl J Med 358 1590 602

32. GoldsteinS

OurmanovI

BrownCR

PlishkaR

Buckler-WhiteA

2005 Plateau levels of viremia correlate with the degree of CD4+-T-cell loss in simian immunodeficiency virus SIVagm-infected pigtailed macaques: variable pathogenicity of natural SIVagm isolates. J Virol 79 5153 5162

33. RambautA

PosadaD

CrandallKA

HolmesEC

2004 The causes and consequences of HIV evolution. Nat Rev Genet 5 52 61

34. AndersonRM

MayRM

1982 Coevolution of hosts and parasites. Parasitology 85 411 426

35. BonhoefferS

FunkGA

GunthardHF

FischerM

MullerV

2003 Glancing behind virus load variation in HIV-1 infection. Trends Microbiol 11 499 504

36. HollingsworthTD

AndersonRM

FraserC

2008 HIV-1 transmission, by stage of infection. J Infect Dis 198 687 693

37. KeetIP

VeugelersPJ

KootM

de WeerdMH

RoosMT

1996 Temporal trends of the natural history of HIV-1 infection following seroconversion between 1984 and 1993. AIDS 10 1601 2

38. AriënKK

TroyerRM

GaliY

ColebundersRL

ArtsEJ

2005 Replicative fitness of historical and recent HIV-1 isolates suggests HIV-1 attenuation over time. AIDS 19 1555 64

39. SiniccoA

ForaR

RaiteriR

SciandraM

BechisG

1997 Is the clinical course of HIV-1 changing? Cohort study. Brit Med J 314 1232 7

40. VanhemsP

LambertJ

GuerraM

HirschelB

AllardR

1999 Association between the rate of CD4+ T cell decrease and the year of human immunodeficiency virus (HIV) type 1 seroconversion among persons enrolled in the Swiss HIV cohort study. J Infect Dis 180 1803 8

41. DorrucciM

RezzaG

PorterK

PhillipsA

Concerted Action on Seroconversion to AIDS and Death in Europe Collaboration 2007 Temporal trends in postseroconversion CD4 cell count and HIV load: the Concerted Action on Seroconversion to AIDS and Death in Europe Collaboration, 1985-2002. J Infect Dis 195 525 34

42. GrasL

JurriaansS

BakkerM

van SighemA

BezemerD

2009 Viral load levels measured at set-point have risen over the last decade of the HIV epidemic in the Netherlands. PLoS One 4 e7365

43. HolmbergSD

ConleyLJ

LubySP

CohnS

WongLC

1995 Recent infection with human immunodeficiency virus and possible rapid loss of CD4 T lymphocytes. J Acquir Immune Defic Syndr Hum Retrovirol 9 291 6

44. O'BrienTR

HooverDR

RosenbergPS

ChenB

DetelsR

1995 Evaluation of secular trends in CD4+ lymphocyte loss among human immunodeficiency virus type 1 (HIV-1)-infected men with known dates of seroconversion. Am J Epidemiol 142 636 42

45. CASCADE Collaboration 2000 Time from HIV-1 seroconversion to AIDS and death before widespread use of highly-active antiretroviral therapy: a collaborative re-analysis. Collaborative Group on AIDS Incubation and HIV Survival including the CASCADE EU Concerted Action. Concerted Action on SeroConversion to AIDS and Death in Europe. Lancet 355 1131 7

46. CASCADE Collaboration 2003 Differences in CD4 cell counts at seroconversion and decline among 5739 HIV-1-infected individuals with well-estimated dates of seroconversion. J Acquir Immune Defic Syndr 34 76 83

47. MüllerV

LedergerberB

PerrinL

KlimkaitT

FurrerH

2006 Stable virulence levels in the HIV epidemic of Switzerland over two decades. AIDS 20 889 894

48. HerbeckJT

GottliebGS

LiX

HuZ

DetelsR

2008 Lack of evidence for changing virulence of HIV-1 in North America. PLoS ONE 3 e1525

49. TroudeP

ChaixML

TranL

DeveauC

SengR

2009 No evidence of a change in HIV-1 virulence since 1996 in France. AIDS 23 1261 7

50. TrachtenbergE

KorberB

SollarsC

KeplerTB

HraberPT

2003 Advantage of rare HLA supertype in HIV disease progression. Nat Med 9 928 35

51. GoulderPJR

WatkinsDI

2008 Impact of MHC class I diversity on immune control of immunodeficiency virus replication. Nat Rev Immunol 8 619 30

52. ParkerJ

RambautA

PybusOG

2008 Correlating viral phenotypes with phylogeny: Accounting for phylogenetic uncertainty. Infect Genet Evol 8 239 246

53. LemeyP

Kosakovsky PondSL

DrummondAJ

PybusOG

ShapiroB

2007 Synonymous substitution rates predict HIV disease progression as a result of underlying replication dynamics. PLoS Comput Biol 3 e29

54. RiederP

JoosB

von WylV

KusterH

GrubeC

2010 HIV-1 transmission after cessation of early antiretroviral therapy among men having sex with men. AIDS 24 1177 1183

55. LedergerberB

von OverbeckJ

EggerM

LuthyR

1994 The Swiss HIV Cohort Study: rationale, organization and selected baseline characteristics. Soz Praventivmed 39 387 394

56. von WylV

YerlyS

BöniJ

BürgisserP

KlimkaitT

2007 Emergence of HIV-1 drug resistance in previously untreated patients initiating combination antiretroviral treatment: a comparison of different regimen types. Arch Intern Med 167 1782 90

57. WolbersM

BucherHC

FurrerH

RickenbachM

CavassiniM

2008 Delayed diagnosis of HIV infection and late initiation of antiretroviral therapy in the Swiss HIV Cohort Study. HIV Med 9 397 405

58. RaboudJM

MontanerJS

ConwayB

HaleyL

SherlockC

1996 Variation in plasma RNA levels, CD4 cell counts, and p24 antigen levels in clinically stable men with human immunodeficiency virus infection. J Infect Dis 174 191 4

59. LylesRH

MuñozA

YamashitaTE

BazmiH

DetelsR

2000 Natural history of human immunodeficiency virus type 1 viremia after seroconversion and proximal to AIDS in a large cohort of homosexual men. Multicenter AIDS Cohort Study. J Infect Dis 181 872 80

60. BeerenwinkelN

DäumerM

OetteM

KornK

HoffmannD

2003 Geno2pheno: Estimating phenotypic drug resistance from HIV-1 genotypes. Nucleic Acids Res 31 3850 5

61. PagelM

1994 Detecting correlated evolution on phylogenies: a general method for the comparative analysis of discrete characters. Proc R Soc Lond B 255 37 45