Modelling the Evolution and Spread of HIV Immune Escape Mutants


During infection with human immunodeficiency virus (HIV), immune pressure from cytotoxic T-lymphocytes (CTLs) selects for viral mutants that confer escape from CTL recognition. These escape variants can be transmitted between individuals where, depending upon their cost to viral fitness and the CTL responses made by the recipient, they may revert. The rates of within-host evolution and their concordant impact upon the rate of spread of escape mutants at the population level are uncertain. Here we present a mathematical model of within-host evolution of escape mutants, transmission of these variants between hosts and subsequent reversion in new hosts. The model is an extension of the well-known SI model of disease transmission and includes three further parameters that describe host immunogenetic heterogeneity and rates of within host viral evolution. We use the model to explain why some escape mutants appear to have stable prevalence whilst others are spreading through the population. Further, we use it to compare diverse datasets on CTL escape, highlighting where different sources agree or disagree on within-host evolutionary rates. The several dozen CTL epitopes we survey from HIV-1 gag, RT and nef reveal a relatively sedate rate of evolution with average rates of escape measured in years and reversion in decades. For many epitopes in HIV, occasional rapid within-host evolution is not reflected in fast evolution at the population level.


Vyšlo v časopise: Modelling the Evolution and Spread of HIV Immune Escape Mutants. PLoS Pathog 6(11): e32767. doi:10.1371/journal.ppat.1001196
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001196

Souhrn

During infection with human immunodeficiency virus (HIV), immune pressure from cytotoxic T-lymphocytes (CTLs) selects for viral mutants that confer escape from CTL recognition. These escape variants can be transmitted between individuals where, depending upon their cost to viral fitness and the CTL responses made by the recipient, they may revert. The rates of within-host evolution and their concordant impact upon the rate of spread of escape mutants at the population level are uncertain. Here we present a mathematical model of within-host evolution of escape mutants, transmission of these variants between hosts and subsequent reversion in new hosts. The model is an extension of the well-known SI model of disease transmission and includes three further parameters that describe host immunogenetic heterogeneity and rates of within host viral evolution. We use the model to explain why some escape mutants appear to have stable prevalence whilst others are spreading through the population. Further, we use it to compare diverse datasets on CTL escape, highlighting where different sources agree or disagree on within-host evolutionary rates. The several dozen CTL epitopes we survey from HIV-1 gag, RT and nef reveal a relatively sedate rate of evolution with average rates of escape measured in years and reversion in decades. For many epitopes in HIV, occasional rapid within-host evolution is not reflected in fast evolution at the population level.


Zdroje

1. PhillipsRE

Rowland-JonesS

NixonDF

GotchFM

EdwardsJP

1991 Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition. Nature 354 453 459

2. BorrowP

LewickiH

WeiX

HorwitzMS

PefferN

1997 Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus. Nat Med 3 205 211

3. PriceDA

GoulderPJ

KlenermanP

SewellAK

EasterbrookPJ

1997 Positive selection of HIV-1 cytotoxic T lymphocyte escape variants during primary infection. Proc Natl Acad Sci U S A 94 1890 1895

4. AsquithB

EdwardsCT

LipsitchM

McLeanAR

2006 Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo. PLoS Biol 4 e90

5. GoonetillekeN

LiuMK

Salazar-GonzalezJF

FerrariG

GiorgiE

2009 The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection. J Exp Med 206 1253 1272

6. AllenTM

AltfeldM

YuXG

O'SullivanKM

LichterfeldM

2004 Selection, transmission, and reversion of an antigen-processing cytotoxic T-lymphocyte escape mutation in human immunodeficiency virus type 1 infection. J Virol 78 7069 7078

7. GoulderPJ

BranderC

TangY

TremblayC

ColbertRA

2001 Evolution and transmission of stable CTL escape mutations in HIV infection. Nature 412 334 338

8. GoulderPJ

PhillipsRE

ColbertRA

McAdamS

OggG

1997 Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS. Nat Med 3 212 217

9. FeeneyME

TangY

RooseveltKA

LeslieAJ

McIntoshK

2004 Immune escape precedes breakthrough human immunodeficiency virus type 1 viremia and broadening of the cytotoxic T-lymphocyte response in an HLA-B27-positive long-term-nonprogressing child. J Virol 78 8927 8930

10. KarlssonAC

IversenAK

ChapmanJM

de OlivieraT

SpottsG

2007 Sequential broadening of CTL responses in early HIV-1 infection is associated with viral escape. PLoS One 2 e225

11. GoepfertPA

LummW

FarmerP

MatthewsP

PrendergastA

2008 Transmission of HIV-1 Gag immune escape mutations is associated with reduced viral load in linked recipients. J Exp Med 205 1009 1017

12. KawashimaY

PfafferottK

FraterJ

MatthewsP

PayneR

2009 Adaptation of HIV-1 to human leukocyte antigen class I. Nature 458 641 645

13. MooreCB

JohnM

JamesIR

ChristiansenFT

WittCS

2002 Evidence of HIV-1 adaptation to HLA-restricted immune responses at a population level. Science 296 1439 1443

14. BhattacharyaT

DanielsM

HeckermanD

FoleyB

FrahmN

2007 Founder effects in the assessment of HIV polymorphisms and HLA allele associations. Science 315 1583 1586

15. PondSL

FrostSD

GrossmanZ

GravenorMB

RichmanDD

2006 Adaptation to different human populations by HIV-1 revealed by codon-based analyses. PLoS Comput Biol 2 e62

16. KiepielaP

LeslieAJ

HoneyborneI

RamduthD

ThobakgaleC

2004 Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA. Nature 432 769 775

17. LeslieAJ

PfafferottKJ

ChettyP

DraenertR

AddoMM

2004 HIV evolution: CTL escape mutation and reversion after transmission. Nat Med 10 282 289

18. LiB

GladdenAD

AltfeldM

KaldorJM

CooperDA

2007 Rapid reversion of sequence polymorphisms dominates early human immunodeficiency virus type 1 evolution. J Virol 81 193 201

19. GeelsMJ

CornelissenM

SchuitemakerH

AndersonK

KwaD

2003 Identification of sequential viral escape mutants associated with altered T-cell responses in a human immunodeficiency virus type 1-infected individual. J Virol 77 12430 12440

20. KelleherAD

LongC

HolmesEC

AllenRL

WilsonJ

2001 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. J Exp Med 193 375 386

21. NowakMA

MayRM

PhillipsRE

Rowland-JonesS

LallooDG

1995 Antigenic oscillations and shifting immunodominance in HIV-1 infections. Nature 375 606 611

22. NowakMA

AndersonRM

McLeanAR

WolfsTF

GoudsmitJ

1991 Antigenic diversity thresholds and the development of AIDS. Science 254 963 969

23. AlthausCL

BonhoefferS

2005 Stochastic interplay between mutation and recombination during the acquisition of drug resistance mutations in human immunodeficiency virus type 1. J Virol 79 13572 13578

24. McLeanAR

EmeryVC

WebsterA

GriffithsPD

1991 Population dynamics of HIV within an individual after treatment with zidovudine. AIDS 5 485 489

25. FrostSD

NijhuisM

SchuurmanR

BoucherCA

BrownAJ

2000 Evolution of lamivudine resistance in human immunodeficiency virus type 1-infected individuals: the relative roles of drift and selection. J Virol 74 6262 6268

26. MarksAJ

PillayD

McLeanAR

2010 The effect of intrinsic stochasticity on transmitted HIV drug resistance patterns. J Theor Biol 262 1 13

27. BrownAJ

RichmanDD

1997 HIV-1: gambling on the evolution of drug resistance? Nat Med 3 268 271

28. PoonAFY

Kosakovsky PondSL

BennettP

RichmanDD

Leigh BrownAJ

2007 Adaptation to human populations is revealed by within-host polymorphisms in HIV-1 and hepatitis C virus. Plos Pathog 3 409 417

29. BaggaleyRF

FergusonNM

GarnettGP

2005 The epidemiological impact of antiretroviral use predicted by mathematical models: a review. Emerg Themes Epidemiol 2 9

30. ThompsonJN

BurdonJJ

1992 Gene-for-gene coevolution between plants and parasites. Nature 360 121 125

31. CromerD

WolinskySM

McLeanAR

2010 How fast could HIV change gene frequencies in the human population? Proc Biol Sci 277 1981 1989

32. FraterAJ

BrownH

OxeniusA

GunthardHF

HirschelB

2007 Effective T-cell responses select human immunodeficiency virus mutants and slow disease progression. J Virol 81 6742 6751

33. SchererA

FraterJ

OxeniusA

AgudeloJ

PriceDA

2004 Quantifiable cytotoxic T lymphocyte responses and HLA-related risk of progression to AIDS. Proc Natl Acad Sci U S A 101 12266 12270

34. OxeniusA

PriceDA

GunthardHF

DawsonSJ

FagardC

2002 Stimulation of HIV-specific cellular immunity by structured treatment interruption fails to enhance viral control in chronic HIV infection. Proc Natl Acad Sci U S A 99 13747 13752

35. DudaA

Lee-TurnerL

FoxJ

RobinsonN

DustanS

2009 HLA-associated clinical progression correlates with epitope reversion rates in early human immunodeficiency virus infection. J Virol 83 1228 1239

36. MarshSGE

ParhamP

BarberLD

2000 The HLA Factsbook: Academic Press

37. Swiss Confederation HIV and AIDS in Switzerland 2006. Federal Office of Public Health. March 2007

38. AndersonRM

MayRM

1991 Infectious diseases of humans: dynamics and control: Oxford and New York: Oxford University Press

39. MorganD

MaheC

MayanjaB

OkongoJM

LubegaR

2002 HIV-1 infection in rural Africa: is there a difference in median time to AIDS and survival compared with that in industrialized countries? AIDS 16 597 603

40. WawerMJ

GrayRH

SewankamboNK

SerwaddaD

LiX

2005 Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis 191 1403 1409

41. HollingsworthTD

AndersonRM

FraserC

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

42. RousseauCM

DanielsMG

CarlsonJM

KadieC

CrawfordH

2008 HLA class I-driven evolution of human immunodeficiency virus type 1 subtype c proteome: immune escape and viral load. J Virol 82 6434 6446

43. 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

44. BonhoefferS

ChappeyC

ParkinNT

WhitcombJM

PetropoulosCJ

2004 Evidence for positive epistasis in HIV-1. Science 306 1547 1550

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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PLOS Pathogens


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