#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Structured Observations Reveal Slow HIV-1 CTL Escape


The cytotoxic T-lymphocyte (CTL) arm of the immune response is thought to play a significant role in the control of HIV-1 infection. Mutations within the HIV-1 genome allow the virus to escape recognition by CTLs and so evade the immune response. These escape mutations have been well documented but observed waiting times to escape within an individual have ranged from days to years. Many studies describing CTL escape have taken a detailed look at a few patients. Our analysis is based on a cohort of 125 clinical trial participants with immunologic and viral sequence data taken at regular longitudinal time points within the first few years of infection. Results suggested that the majority of CTL-related mutations present early in infection had been transmitted in the infecting viral strain as opposed to arising in the new host due to selection pressure imposed by CTLs. Whilst the prevalence of CTL escape mutations in the dataset was high, the incidence of new escape was relatively low; around one third of patients did not drive an escape within the first two years. Patients possessing a ‘protective’ HLA genotype had a significantly shorter waiting time to first escape than those without.


Vyšlo v časopise: Structured Observations Reveal Slow HIV-1 CTL Escape. PLoS Genet 11(2): e32767. doi:10.1371/journal.pgen.1004914
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004914

Souhrn

The cytotoxic T-lymphocyte (CTL) arm of the immune response is thought to play a significant role in the control of HIV-1 infection. Mutations within the HIV-1 genome allow the virus to escape recognition by CTLs and so evade the immune response. These escape mutations have been well documented but observed waiting times to escape within an individual have ranged from days to years. Many studies describing CTL escape have taken a detailed look at a few patients. Our analysis is based on a cohort of 125 clinical trial participants with immunologic and viral sequence data taken at regular longitudinal time points within the first few years of infection. Results suggested that the majority of CTL-related mutations present early in infection had been transmitted in the infecting viral strain as opposed to arising in the new host due to selection pressure imposed by CTLs. Whilst the prevalence of CTL escape mutations in the dataset was high, the incidence of new escape was relatively low; around one third of patients did not drive an escape within the first two years. Patients possessing a ‘protective’ HLA genotype had a significantly shorter waiting time to first escape than those without.


Zdroje

1. McMichael AJ, Borrow P, Tomaras GD, Goonetilleke N, Haynes BF (2010) The immune response during acute HIV-1 infection: clues for vaccine development. Nat Rev Immunol 10: 11–23. doi: 10.1038/nri2674 20010788

2. Goonetilleke N, Liu MK, Salazar-Gonzalez JF, Ferrari G, Giorgi E, et al. (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. doi: 10.1084/jem.20090365 19487423

3. Kiepiela P, Ngumbela K, Thobakgale C, Ramduth D, Honeyborne I, et al. (2006) CD8+ T-cell responses to different HIV proteins have discordant associations with viral load. Nat Med 13: 46–53. doi: 10.1038/nm1520 17173051

4. Pereyra F, Jia X, McLaren PJ, Telenti A, De Bakker P, et al. (2010) The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science 330: 1551–1557. doi: 10.1126/science.1195271 21051598

5. Fellay J, Shianna KV, Ge D, Colombo S, Ledergerber B, et al. (2007) A whole-genome association study of major determinants for host control of HIV-1. Science 317: 944–947. doi: 10.1126/science.1143767 17641165

6. Altfeld M, Kalife ET, Qi Y, Streeck H, Lichterfeld M, et al. (2006) HLA Alleles Associated with Delayed Progression to AIDS Contribute Strongly to the Initial CD8+ T Cell Response against HIV-1. PLoS Med 3: e403+. doi: 10.1371/journal.pmed.0030403 17076553

7. Schmitz JE, Kuroda MJ, Santra S, Sasseville VG, Simon MA, et al. (1999) Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 283: 857–860. doi: 10.1126/science.283.5403.857 9933172

8. Wong JK, Strain MC, Porrata R, Reay E, Sankaran-Walters S, et al. (2010) In vivo CD8+ T-cell suppression of SIV viremia is not mediated by CTL clearance of productively infected cells. PLoS Pathog 6: e1000748. doi: 10.1371/journal.ppat.1000748 20126442

9. Kaiser P, Joos B, Niederöst B, Weber R, Günthard HF, et al. (2007) Productive human immunodeficiency virus type 1 infection in peripheral blood predominantly takes place in CD4/CD8 double-negative T lymphocytes. J Virol 81: 9693–9706. doi: 10.1128/JVI.00492-07 17609262

10. Asquith B, Edwards CTT, Lipsitch M, McLean AR (2006) Inefficient Cytotoxic T Lymphocyte-Mediated Killing of HIV-1Infected Cells In Vivo. PLoS Biol 4: e90+. doi: 10.1371/journal.pbio.0040090 16515366

11. Kelleher AD, Long C, Holmes EC, Allen RL, Wilson J, et al. (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. doi: 10.1084/jem.193.3.375 11157057

12. Phillips RE, Rowland-Jones S, Nixon DF, Gotch FM, Edwards JP, et al. (1991) Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition. Nature 354: 453–459. doi: 10.1038/354453a0 1721107

13. Price DA, Goulder PJ, Klenerman P, Sewell AK, Easterbrook PJ, et al. (1997) Positive selection of HIV-1 cytotoxic T lymphocyte escape variants during primary infection. Proc Natl Acad Sci U S A 94: 1890–1895. doi: 10.1073/pnas.94.5.1890 9050875

14. Zimbwa P, Milicic A, Frater J, Scriba TJ, Willis A, et al. (2007) Precise identification of a human immunodeficiency virus type 1 antigen processing mutant. J Virol 81: 2031–2038. doi: 10.1128/JVI.00968-06 17108020

15. Allen TM, Altfeld M, Geer SC, Kalife ET, Moore C, et al. (2005) Selective Escape from CD8+ T-Cell Responses Represents a Major Driving Force of Human Immunodeficiency Virus Type 1 (HIV-1) Sequence Diversity and Reveals Constraints on HIV-1 Evolution. J Virol 79: 13239–13249. doi: 10.1128/JVI.79.21.13239-13249.2005 16227247

16. Henn MR, Boutwell CL, Charlebois P, Lennon NJ, Power KA, et al. (2012) Whole genome deep sequencing of HIV-1 reveals the impact of early minor variants upon immune recognition during acute infection. PLoS Pathog 8: e1002529. doi: 10.1371/journal.ppat.1002529 22412369

17. Jones NA, Wei X, Flower DR, Wong M, Michor F, et al. (2004) Determinants of human immunodeficiency virus type 1 escape from the primary CD8+ cytotoxic T lymphocyte response. J Exp Med 200: 1243–1256. doi: 10.1084/jem.20040511 15545352

18. Fischer W, Ganusov VV, Giorgi EE, Hraber PT, Keele BF, et al. (2010) Transmission of single HIV-1 genomes and dynamics of early immune escape revealed by ultra-deep sequencing. PloS One 5: e12303. doi: 10.1371/journal.pone.0012303 20808830

19. Liu MK, Hawkins N, Ritchie AJ, Ganusov VV, Whale V, et al. (2013) Vertical T cell immunodominance and epitope entropy determine HIV-1 escape. J Clin Invest 123: 380. doi: 10.1172/JCI65330 23221345

20. Duda A, Lee-Turner L, Fox J, Robinson N, Dustan S, et al. (2009) HLA-associated clinical progression correlates with epitope reversion rates in early human immunodeficiency virus infection. J Virol 83: 1228–1239. doi: 10.1128/JVI.01545-08 19019964

21. Jamieson BD, Yang OO, Hultin L, Hausner MA, Hultin P, et al. (2003) Epitope escape mutation and decay of human immunodeficiency virus type 1-specific CTL responses. J Immunol 171: 5372–5379. doi: 10.4049/jimmunol.171.10.5372 14607940

22. Geels MJ, Cornelissen M, Schuitemaker H, Anderson K, Kwa D, et al. (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. doi: 10.1128/JVI.77.23.12430-12440.2003 14610167

23. Fryer HR, Frater J, Duda A, Roberts MG, Phillips RE, et al. (2010) Modelling the evolution and spread of HIV immune escape mutants. PLoS Pathog 6: e1001196. doi: 10.1371/journal.ppat.1001196 21124991

24. Brumme ZL, Brumme CJ, Carlson J, Streeck H, John M, et al. (2008) 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. J Virol 82: 9216–9227. doi: 10.1128/JVI.01041-08 18614631

25. Goulder PJ, Watkins DI (2004) HIV and SIV CTL escape: implications for vaccine design. Nat Rev Immunol 4: 630–640. doi: 10.1038/nri1417 15286729

26. Klenerman P, Hill A (2005) T cells and viral persistence: lessons from diverse infections. Nat Immunol 6: 873–879. doi: 10.1038/ni1241 16116467

27. Chopera DR, Mlotshwa M, Woodman Z, Mlisana K, de Assis Rosa D, et al. (2011) Virological and immunological factors associated with HIV-1 differential disease progression in HLA-B* 58: 01-positive individuals. J Virol 85: 7070–7080. doi: 10.1128/JVI.02543-10 21613398

28. Herbeck JT, Rolland M, Liu Y, McLaughlin S, McNevin J, et al. (2011) Demographic processes affect HIV-1 evolution in primary infection before the onset of selective processes. J Virol 85: 7523–7534. doi: 10.1128/JVI.02697-10 21593162

29. Oxenius A, Price DA, Trkola A, Edwards C, Gostick E, et al. (2004) Loss of viral control in early HIV-1 infection is temporally associated with sequential escape from CD8+ T cell responses and decrease in HIV-1-specific CD4+ and CD8+ T cell frequencies. J Infect Dis 190: 713–721. doi: 10.1086/422760 15272399

30. Cao J, McNevin J, Holte S, Fink L, Corey L, et al. (2003) Comprehensive analysis of human immunodeficiency virus type 1 (HIV-1)-specific gamma interferon-secreting CD8+ T cells in primary HIV-1 infection. J Virol 77: 6867–6878. doi: 10.1128/JVI.77.12.6867-6878.2003 12768006

31. Leslie A, Pfafferott K, Chetty P, Draenert R, Addo M, et al. (2004) HIV evolution: CTL escape mutation and reversion after transmission. Nat Med 10: 282–289. doi: 10.1038/nm992 14770175

32. Fidler S, Porter K, Ewings F, Frater J, Ramjee G, et al. (2013) Short-course antiretroviral therapy in primary HIV infection. N Engl J Med 368: 207–217. doi: 10.1056/NEJMoa1110039 23323897

33. Ferrari G, Korber B, Goonetilleke N, Liu MK, Turnbull EL, et al. (2011) 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. doi: 10.1371/journal.ppat.1001273 21347345

34. Liu Y, McNevin J, Cao J, Zhao H, Genowati I, et al. (2006) Selection on the human immunodeficiency virus type 1 proteome following primary infection. J Virol 80: 9519–9529. doi: 10.1128/JVI.00575-06 16973556

35. Salazar-Gonzalez JF, Salazar MG, Keele BF, Learn GH, Giorgi EE, et al. (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. doi: 10.1084/jem.20090378 19487424

36. Ganusov VV, Goonetilleke N, Liu MK, Ferrari G, Shaw GM, et al. (2011) Fitness costs and diversity of the cytotoxic T lymphocyte (CTL) response determine the rate of CTL escape during acute and chronic phases of HIV infection. J Virol 85: 10518–10528. doi: 10.1128/JVI.00655-11 21835793

37. Frater AJ, Brown H, Oxenius A, Günthard H, Hirschel B, et al. (2007) Effective T-cell responses select human immunodeficiency virus mutants and slow disease progression. J Virol 81: 6742–6751. doi: 10.1128/JVI.00022-07 17409157

38. Asquith B (2008) The Evolutionary Selective Advantage of HIV-1 Escape Variants and the Contribution of Escape to the HLA-Associated Risk of AIDS Progression. PLoS One 3: e3486. doi: 10.1371/journal.pone.0003486 18941529

39. Palmer D, Frater J, Phillips R, McLean AR, McVean G (2013) Integrating genealogical and dynamical modelling to infer escape and reversion rates in HIV epitopes. Proc Biol Sci 280. doi: 10.1098/rspb.2013.0696

40. Llano A, Williams A, Olvera A, Silva-Arrieta S, Brander C (2013) Best-Characterized HIV-1 CTL Epitopes: The 2013 Update. HIV Molecular Immunology 2013: 3–25.

41. Frahm N, Yusim K, Suscovich TJ, Adams S, Sidney J, et al. (2007) Extensive HLA class I allele promiscuity among viral CTL epitopes. Eur J Immunol 37: 2419–2433. doi: 10.1002/eji.200737365 17705138

42. Fryer HR, Frater J, Duda A, Palmer D, Phillips RE, et al. (2012) Cytotoxic T-lymphocyte escape mutations identified by HLA association favor those which escape and revert rapidly. J Virol 86: 8568–8580. doi: 10.1128/JVI.07020-11 22674992

43. English S, Katzourakis A, Bonsall D, Flanagan P, Duda A, et al. (2011) Phylogenetic analysis consistent with a clinical history of sexual transmission of HIV-1 from a single donor reveals transmission of highly distinct variants. Retrovirology 8: 54. doi: 10.1186/1742-4690-8-54 21736738

44. Frater J, Ewings F, Hurst J, Brown H, Robinson N, et al. (2014) HIV-1 specific CD4 responses in primary HIV-1 infection predict disease progression in the SPARTAC trial. AIDS.

45. Los Alamos National Laboratory (2013). HIV Molecular Immunology Database. URL http://www.hiv.lanl.gov/content/immunology.

46. Schellens IM, Kesmir C, Miedema F, van Baarle D, Borghans JA (2008) An unanticipated lack of consensus cytotoxic T lymphocyte epitopes in HIV-1 databases: the contribution of prediction programs. AIDS 22: 33–37. doi: 10.1097/QAD.0b013e3282f15622 18090389

47. O'Brien SJ, Gao X, Carrington M (2001) HLA and AIDS: a cautionary tale. Trends Mol Med 7: 379–381. doi: 10.1016/S1471-4914(01)02131-1 11530315

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2015 Číslo 2
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#