Influence of HAART on Alternative Reading Frame Immune Responses over the Course of HIV-1 Infection

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art_HONG_Influence_of_HAART_on_Alternative_Reading_Frame_Immune_2012.PDF (1.61 MB)
Citações na Scopus
16
Tipo de produção
article
Data de publicação
2012
Editora
PUBLIC LIBRARY SCIENCE
DOI
Indexadores
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Autores
CHAMPIAT, Stephane
RAPOSO, Rui Andre Saraiva
MANESS, Nicholas J.
LEHMAN, John L.
PURTELL, Sean E.
HASENKRUG, Aaron M.
MILLER, Jacob C.
DEAN, Hansi
KOFF, Wayne C.
Autor de Grupo de pesquisa
Editores
Coordenadores
Organizadores
Citação
PLOS ONE, v.7, n.6, article ID e39311, 13p, 2012
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Background: Translational errors can result in bypassing of the main viral protein reading frames and the production of alternate reading frame (ARF) or cryptic peptides. Within HIV, there are many such ARFs in both sense and the antisense directions of transcription. These ARFs have the potential to generate immunogenic peptides called cryptic epitopes (CE). Both antiretroviral drug therapy and the immune system exert a mutational pressure on HIV-1. Immune pressure exerted by ARF CD8(+) T cells on the virus has already been observed in vitro. HAART has also been described to select HIV-1 variants for drug escape mutations. Since the mutational pressure exerted on one location of the HIV-1 genome can potentially affect the 3 reading frames, we hypothesized that ARF responses would be affected by this drug pressure in vivo. Methodology/Principal findings: In this study we identified new ARFs derived from sense and antisense transcription of HIV-1. Many of these ARFs are detectable in circulating viral proteins. They are predominantly found in the HIV-1 env nucleotide region. We measured T cell responses to 199 HIV-1 CE encoded within 13 sense and 34 antisense HIV-1 ARFs. We were able to observe that these ARF responses are more frequent and of greater magnitude in chronically infected individuals compared to acutely infected patients, and in patients on HAART, the breadth of ARF responses increased. Conclusions/Significance: These results have implications for vaccine design and unveil the existence of potential new epitopes that could be included as vaccine targets.
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https://observatorio.fm.usp.br/handle/OPI/2486
Referências
  1. Addo MM, 2001, P NATL ACAD SCI USA, V98, P1781, DOI 10.1073/pnas.98.4.1781
  2. Addo MM, 2003, J VIROL, V77, P2081, DOI 10.1128/JVI.77.3.2081-2092.2003
  3. Altfeld M, 2001, J IMMUNOL, V167, P2743
  4. Bansal A, 2010, J EXP MED, V207, P51, DOI 10.1084/jem.20092060
  5. Berger CT, 2010, J EXP MED, V207, P61, DOI 10.1084/jem.20091808
  6. Betts MR, 2001, J VIROL, V75, P11983, DOI 10.1128/JVI.75.24.11983-11991.2001
  7. BORROW P, 1994, J VIROL, V68, P6103
  8. BRUCE AG, 1986, P NATL ACAD SCI USA, V83, P5062, DOI 10.1073/pnas.83.14.5062
  9. Bullock TNJ, 1997, J EXP MED, V186, P1051, DOI 10.1084/jem.186.7.1051
  10. Bullock TNJ, 1996, J EXP MED, V184, P1319, DOI 10.1084/jem.184.4.1319
  11. Cardinaud S, 2004, J EXP MED, V199, P1053, DOI 10.1084/jem.20031869
  12. FETTEN JV, 1991, J IMMUNOL, V147, P2697
  13. Friedrich TC, 2007, J VIROL, V81, P3465, DOI 10.1128/JVI.02392-06
  14. Garrison KE, 2009, CLIN VACCINE IMMUNOL, V16, P1369, DOI 10.1128/CVI.00410-08
  15. Gatanaga H, 2010, AIDS, V24, pF15, DOI 10.1097/QAD.0b013e328337b010
  16. Goepfert PA, 2008, J EXP MED, V205, P1009, DOI 10.1084/jem.20072457
  17. Ho O, 2006, J IMMUNOL, V176, P2470
  18. Jin X, 1999, J EXP MED, V189, P991, DOI 10.1084/jem.189.6.991
  19. John M, 2005, ANTIVIR THER, V10, P551
  20. Karlsson AC, 2003, J VIROL, V77, P6743, DOI 10.1128/JVI.77.12.6743-6752.2003
  21. Kiepiela P, 2007, NAT MED, V13, P46, DOI 10.1038/nm1520
  22. Landry S, 2007, RETROVIROLOGY, V4, DOI 10.1186/1742-4690-4-71
  23. Liu JY, 2009, NATURE, V457, P87, DOI 10.1038/nature07469
  24. Ludwig LB, 2006, RETROVIROLOGY, V3, DOI 10.1186/1742-4690-3-80
  25. Mahnke Lisa, 2006, AIDS Res Ther, V3, P21, DOI 10.1186/1742-6405-3-21
  26. Malarkannan S, 1999, IMMUNITY, V10, P681, DOI 10.1016/S1074-7613(00)80067-9
  27. Maness NJ, 2007, J EXP MED, V204, P2505, DOI 10.1084/jem.20071261
  28. Maness NJ, 2009, J VIROL, V83, P10280, DOI 10.1128/JVI.00138-09
  29. Maness NJ, 2010, J IMMUNOL, V184, P67, DOI 10.4049/jimmunol.0903118
  30. Manosuthi W, AIDS, V24, P411
  31. Masemola A, 2004, J VIROL, V78, P3233, DOI 10.1128/JVI.78.7.3233-3243.2004
  32. Mason RA, 2004, J IMMUNOL, V172, P7212
  33. Mayrand SM, 1998, IMMUNOL TODAY, V19, P551, DOI 10.1016/S0167-5699(98)01342-5
  34. McBratney S, 1993, CURR OPIN CELL BIOL, V5, P961, DOI 10.1016/0955-0674(93)90077-4
  35. McElrath MJ, 2008, LANCET, V372, P1894, DOI 10.1016/S0140-6736(08)61592-5
  36. Meiklejohn DA, 2004, J IMMUNOL METHODS, V288, P135, DOI 10.1016/j.jim.2004.03.006
  37. MICHAEL NL, 1994, J VIROL, V68, P979
  38. Mueller SM, 2011, JAIDS-J ACQ IMM DEF, V56, P109, DOI 10.1097/QAI.0b013e3181fe946e
  39. Mueller SM, 2007, J VIROL, V81, P2887, DOI 10.1128/JVI.0154'7-06
  40. Novitsky V, 2002, J VIROL, V76, P10155, DOI 10.1128/JVI.76.20.10155-10168.2002
  41. Probst-Kepper M, 2001, J EXP MED, V193, P1189, DOI 10.1084/jem.193.10.1189
  42. Rimoldi D, 2000, J IMMUNOL, V165, P7253
  43. Saeterdal I, 2001, P NATL ACAD SCI USA, V98, P13255
  44. Samri A, 2000, J VIROL, V74, P9306, DOI 10.1128/JVI.74.19.9306-9312.2000
  45. Saulquin X, 2002, J EXP MED, V195, P353, DOI 10.1084/jem.20011399
  46. Schmitt M, 2000, AIDS, V14, P653, DOI 10.1097/00002030-200004140-00004
  47. Schmitz JE, 1999, SCIENCE, V283, P857, DOI 10.1126/science.283.5403.857
  48. Schwab SR, 2004, PLOS BIOL, V2, P1774, DOI 10.1371/journal.pbio.0020366
  49. Wang RF, 1996, J EXP MED, V183, P1131, DOI 10.1084/jem.183.3.1131
  50. WEISS RB, 1987, COLD SPRING HARB SYM, V52, P687
  51. Yu XG, 2002, J VIROL, V76, P8690, DOI 10.1128/JVI.76.17.8690-8701.2002

Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
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