In the present study, we analyzed the functional profile of CD8+ T-cell responses directed against autologous transmitted/founder HIV-1 isolates during acute and early infection, and examined whether multifunctionality is required for selection of virus escape mutations. Seven anti-retroviral therapy-naïve subjects were studied in detail between 1 and 87 weeks following onset of symptoms of acute HIV-1 infection. Synthetic peptides representing the autologous transmitted/founder HIV-1 sequences were used in multiparameter flow cytometry assays to determine the functionality of HIV-1-specific CD8+ T memory cells. In all seven patients, the earliest T cell responses were predominantly oligofunctional, although the relative contribution of multifunctional cell responses increased significantly with time from infection. Interestingly, only the magnitude of the total and not of the poly-functional T-cell responses was significantly associated with the selection of escape mutants. However, the high contribution of MIP-1β-producing CD8+ T-cells to the total response suggests that mechanisms not limited to cytotoxicity could be exerting immune pressure during acute infection. Lastly, we show that epitope entropy, reflecting the capacity of the epitope to tolerate mutational change and defined as the diversity of epitope sequences at the population level, was also correlated with rate of emergence of escape mutants.
Vyšlo v časopise: Relationship between Functional Profile of HIV-1 Specific CD8 T Cells and Epitope Variability with the Selection of Escape Mutants in Acute HIV-1 Infection. PLoS Pathog 7(2): e32767. doi:10.1371/journal.ppat.1001273 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001273
1. DouekDC
KwongPD
NabelGJ
2006
The rational design of an AIDS vaccine.
Cell
124
677
681
2. AppayV
DouekD
PriceD
2008
CD8+ T cell efficacy in vaccination and disease.
Nat Med
3. BorrowP
LewickiH
HahnBH
ShawGM
OldstoneMBA
1994
Virus-specific CD8+ cytotoxic T lymphocyte activity associated with control viremia in primary human immunodeficiency virus type 1 infection.
J Virol
68
6103
6110
4. KoupRA
SafritJF
CaoY
AndrewsCA
McLeodG
Temporal association of cellular immune response with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome.
4650
4655
5. SafritJT
ZhuT
HoDD
KoupRA
Characterization of human immunodeficiency virus type 1-specific cytotoxic T lymphocyte clones isolated during acute seroconversion: recognition of autologous virus sequences within a conserved immunodominant epitope.
J Exp Med
179
463
472
6. GoonetillekeN
LiuMKP
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.
206
1253
1272
7. PhillipsRE
Rowland-JonesS
NixonDF
GotchFM
EdwardsJP
1991
Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition.
Nature
354
453
459
8. BorrowP
WeiX
HorwitzMS
PefferN
1997
Antiviral pressure exerted by HIV-1-specific cytotoxic T limphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus.
3
205
217
9. PriceDA
GoulderPJ
KlenermanP
SewellAK
EasterbrookPJ
Positive selection of HIV-1 cytotoxic T lymphocyte escape variants during primary infection.
Proc Natl Acad Sci USA
94
1890
1895
10. GoulderPJ
WatkinsDI
2004
HIV and SIV CTL escape: implications for vaccine design.
Nat Rev Immunol
4
630
640
11. GoulderPJ
PhillipsRE
ColbertRA
McAdamS
OggG
Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS.
212
12. FeeneyME
TangY
RooseveltKA
LeslieAJ
McIntoshK
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.
78
8927
8930
13. AllenTM
O'ConnorDH
JingP
DzurisJL
MotheBR
2000
Tat-specific cytotoxic T lymphocytes select for SIV escape variants during resolution of primary viraemia [see comments].
407
386
390
14. O'ConnorDH
AllenTM
VogelTU
DeSouzaIP
2002
Acute phase cytotoxic T lymphocyte escape is a hallmark of simian immunodeficiency virus infection.
8
493
499
15. BarouchDH
KunstmanJ
KurodaMJ
SchmitzJE
SantraS
Eventual AIDS vaccine failure in a rhesus monkey by viral escape from cytotoxic T lymphocytes.
415
335
339
16. Martinez-PicadoJ
PradoJG
FryEE
PfafferottK
LeslieA
Fitness cost of escape mutations in p24 Gag in association with control of human immunodeficiency virus type 1.
80
3617
3623
17. LiB
GladdenAD
AltfeldM
KaldorJM
CooperDA
2007
Rapid reversion of sequence polymorphisms dominates early human immunodeficiency virus type 1 evolution.
81
193
201
18. Sanchez-MerinoV
FarrowMA
BrewsterF
SomasundaranM
LuzuriagaK
Identification and characterization of HIV-1 CD8+ T cell escape variants with impaired fitness.
J Infect Dis
197
300
308
19. BoutwellCL
RowleyCF
EssexM
Reduced viral replication capacity of human immunodeficiency virus type 1 subtype C caused by cytotoxic-T-lymphocyte escape mutations in HLA-B57 epitopes of capsid protein.
83
2460
2468
20. GanusovV
de BoerR
Estimating costs and benefits of CTL escape mutations in SIV/HIV infection.
PLoS Comput Biol
21. LohL
BattenCJ
PetravicJ
DavenportMP
KentSJ
In vivo fitness costs of different Gag CD8 T-cell escape mutant simian-human immunodeficiency viruses for macaques.
5418
5422
22. ZimmerliSC
HarariA
CelleraiC
VallelianF
BartPA
2005
HIV-1-specific IFN-gamma/IL-2-secreting CD8 T cells support CD4-independent proliferation of HIV-1-specific CD8 T cells.
Proc Natl Acad Sci U S A
102
7239
7244
23. BettsMR
NasonMC
WestSM
De RosaSC
MiguelesSA
HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells.
Blood
107
4781
4789
24. FisherW
GanusovV
HraberP
KeeleBF
2010
Transmission of Single HIV-1 Genomes and Dynamics of Early Immune Escape Revealed by Ultra-deep Sequencing.
PLoS One
25. BurgersWA
RiouC
MlotshwaM
MaenetjeP
de Assis RosaD
Association of HIV-specific and total CD8+ T memory phenotypes in subtype C HIV-1 infection with viral set point.
J Immunol
182
4751
4761
26. TurnbullEL
WongM
WangS
JonesNA
Kinetics of expansion of epitope-specific T cell responses during primary HIV-1 infection.
7131
7145
27. McElrathMJ
MoodieZ
DubeyS
KiersteadL
HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case-cohort analysis.
Lancet
372
1894
1905
28. Rerks-NgarmS
PitisuttithumP
NitayaphanS
KaewkungwalJ
ChiuJ
Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand.
N Engl J Med
361
2209
2220
29. CoreyL
McElrathMJ
KublinJG
Post-step modifications for research on HIV vaccines.
AIDS
23
30. LiuJ
O'BrienKL
LynchDM
SimmonsNL
La PorteA
Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys.
457
87
91
31. ReynoldsMR
WeilerAM
WeisgrauKL
PiaskowskiSM
FurlottJR
Macaques vaccinated with live-attenuated SIV control replication of heterologous virus.
2537
2550
32. HansenSG
VievilleC
WhizinN
Coyne-JohnsonL
SiessDC
Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge.
15
293
299
33. McMichaelAJ
BorrowP
TomarasGD
GoonetillekeN
HaynesBF
The immune response during acute HIV-1 infection: clues for vaccine development.
10
11
34. CritchfieldJW
YoungDH
HayesTL
BraunJV
GarciaJC
Magnitude and complexity of rectal mucosa HIV-1-specific CD8+ T-cell responses during chronic infection reflect clinical status.
PLoS ONE
e3577
35. StreeckH
BrummeZL
AnastarioM
CohenKW
JolinJS
Antigen load and viral sequence diversification determine the functional profile of HIV-1-specific CD8+ T cells.
PLoS Med
5
e100
36. TrautmannL
JanbazianL
ChomontN
SaidE
Upregulation of PD-1 expression on HIV-specific CD8 T cells leads to reversible immune dysfunction.
37. PetrovasC
CasazzaJP
BrenchleyJM
PriceDA
GostickE
PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection.
203
2281
2292
38. PrecopioML
BettsMR
ParrinoJ
Immunization with vaccinia virus induces polyfunctional and phenotypically distinctive CD8(+) T cell responses.
204
1405
1416
39. BrummeZL
BrummeCJ
CarlsonJ
StreeckH
JohnM
Marked epitope - and allele-specific differences in rates of mutation in human immunodeficiency type 1 (HIV-1) Gag, Pol, and Nef cytotoxic T-lymphocyte epitopes in acute/early HIV-1 infection.
82
9216
9227
40. GallimoreA
DumreseT
HengartnerH
ZinkernagelRM
RammenseeHG
1998
Protective immunity does not correlate with the hierarchy of virus - specific cytotoxic T cell responses to naturally processed peptides.
187
1647
1657
41. AlmeidaJR
PapagnoL
ArkoubZA
SauceD
Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover.
2473
2485
42. AlmeidaJR
ShinSY
Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and HIV-suppressive activity.
113
6351
6360
43. PriceDA
AsherTE
WilsonNA
Public clonotype usage identifies protective Gag-specific CD8+ T cell responses in SIV infection.
923
936
44. AppayV
van LierR
SallustoF
RoedererM
Phenotype and function of human T lymphocyte subsets: Consensus and issues.
Cytometry Part B: Clinical Cytometry
45. FreelSA
LamoreauxL
ChattopadhyayPK
SaundersK
ZarkowskyD
Phenotypic and Functional Profile of HIV-inhibitory CD8 T cells Elicited by Natural Infection and Heterologous Prime/boost Vaccination.
46. CocchiF
DeVicoAL
Garzino-DemoA
AryaSK
GalloRC
1995
Identification of RANTES, MIP-1αand MIP-1β as the major HIV-suppressive factors produced by CD8+ T cells.
Science
270
1811
1815
47. SaundersKO
Ward-CavinessC
SchutteRJ
FreelSA
OvermanRG
Secretion of MIP-1β and MIP-1α by CD8(+) T-lymphocytes correlates with HIV-1 inhibition independent of coreceptor usage.
Cellular immunology
48. SaundersKO
CunninghamCK
Epigenetic regulation of CD8(+) T-lymphocyte mediated suppression of HIV-1 replication.
Virology
405
234
242
49. WongJK
StrainMC
PorrataR
ReayE
Sankaran-WaltersS
In vivo CD8+ T-cell suppression of siv viremia is not mediated by CTL clearance of productively infected cells.
PLoS Pathog
6
e1000748
50. KlattNR
ShudoE
OrtizAM
EngramJC
PaiardiniM
CD8+ lymphocytes control viral replication in SIVmac239-infected rhesus macaques without decreasing the lifespan of productively infected cells.
e1000747
51. BansalA
GoughE
SabbajS
RitterD
YusimK
CD8 T-cell responses in early HIV-1 infection are skewed towards high entropy peptides.
19
241
250
52. JonesNA
FlowerDR
MichorF
Determinants of human immunodeficiency virus type 1 escape from the primary CD8+ cytotoxic T lymphocyte response.
200
1243
1256
53. FiebigEW
WrightDJ
RawalBD
GarrettPE
SchumacherRT
2003
Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection.
17
1871
1879
54. Salazar-GonzalezJF
SalazarMG
LearnGH
GiorgiEE
Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection.
1273
1289
55. ShannonCE
1948
A mathematical Theory of Communication".
Bell System Technical Journal
27
379
423, 623-656
56. Fontaine CostaAI
RaoX
LechenadecE
van BaarleD
KeşmirC
HLA-B molecules target more conserved regions of the HIV-1 proteome.
24
211
215
57. KorberBT
KunstmanKJ
PattersonBK
FurtadoM
McEvillyMM
Genetic differences between blood - and brain-derived viral sequences from human immunodeficiency virus type 1-infected patients: evidence of conserved elements in the V3 region of the envelope protein of brain-derived sequences.
7467
7481
Zvýšte si kvalifikáciu online z pohodlia domova
Nemáte účet? Registrujte sa
Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.
