Frequent associations between CTL and T-Helper epitopes in HIV-1 genomes and implications for multi-epitope vaccine designs

BMC Microbiology

Volumn 10, Issue , 2010, Pages

  Paul, Sinu ^a   Piontkivska, Helen ^a  

^a KENT STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EPITOPE; VIRUS ANTIGEN; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; VIRUS PROTEIN;

AMINO ACID SEQUENCE; ARTICLE; CYTOTOXIC T LYMPHOCYTE; HELPER CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; NONHUMAN; NUCLEOTIDE SEQUENCE; REGULATOR GENE; STRUCTURAL GENE; VIRUS GENE; VIRUS GENOME; CHEMISTRY; GENETICS; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOLOGY; MOLECULAR GENETICS; VIROLOGY;

HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1;

AIDS VACCINES; AMINO ACID SEQUENCE; EPITOPES, T-LYMPHOCYTE; GENOME, VIRAL; HIV INFECTIONS; HIV-1; HUMANS; MOLECULAR SEQUENCE DATA; T-LYMPHOCYTES, CYTOTOXIC; VIRAL PROTEINS;

EID: 77955289219     PISSN: 14712180     EISSN: 14712180     Source Type: Journal    
DOI: 10.1186/1471-2180-10-212     Document Type: Article

References (116)

1. Progress towards development of an HIV vaccine: report of the AIDS Vaccine 2009 Conference. AL Ross A Brave G Scarlatti A Manrique L Buonaguro, The Lancet Infectious Diseases 2010 10 5 305 316 10.1016/S1473-3099(10)70069-4 20417413
2. The survival benefits of AIDS treatment in the United States. RP Walensky AD Paltiel E Losina LM Mercincavage BR Schackman PE Sax MC Weinstein KA Freedberg, J Infect Dis 2006 194 1 11 19 10.1086/505147 16741877
3. Trends in AIDS-defining and non-AIDS-defining malignancies among HIV-infected patients: 1989-2002. R Bedimo RY Chen NA Accortt JL Raper C Linn JJ Allison J Dubay MS Saag CJ Hoesley, Clinical Infectious Diseases 2004 39 9 1380 1384 10.1086/424883 15494916
4. Insulin resistance, glucose intolerance and diabetes mellitus in HIV-infected patients. D Florescu DP Kotler, Antivir Ther 2007 12 2 149 162 17503657
5. Antiretroviral-drug resistance among patients recently infected with HIV. SJ Little S Holte JP Routy ES Daar M Markowitz AC Collier RA Koup JW Mellors E Connick B Conway, N Engl J Med 2002 347 6 385 394 10.1056/NEJMoa013552 12167680
6. Early establishment of a pool of latently infected, resting CD4 T cells during primary HIV-1 infection. TW Chun D Engel MM Berrey T Shea L Corey AS Fauci, Proceedings of the National Academy of Sciences 1998 95 15 8869 8873 10.1073/pnas.95.15.8869 (Pubitemid 28350581)
7. Prevalence of antiretroviral drug resistance and resistance-associated mutations in antiretroviral therapy-naive HIV-infected individuals from 40 United States cities. L Ross ML Lim Q Liao B Wine AE Rodriguez W Weinberg M Shaefer, HIV Clinical Trials 2007 8 1 1 8 10.1310/hct0801-1 17434843
8. HIV drug resistance. F Clavel AJ Hance, N Engl J Med 2004 350 10 1023 1035 14999114
9. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. G Hutter D Nowak M Mossner S Ganepola A Mussig K Allers T Schneider J Hofmann C Kucherer O Blau, N Engl J Med 2009 360 7 692 698 10.1056/NEJMoa0802905 19213682
10. HIV/AIDS research. Surprising AIDS vaccine success praised and pondered. J Cohen, Science 2009 326 5949 26 27 10.1126/science.326-26 19797628
11. Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand. S Rerks-Ngarm P Pitisuttithum S Nitayaphan J Kaewkungwal J Chiu R Paris N Premsri C Namwat M de Souza E Adams, N Engl J Med 2009 361 23 2209 2220 10.1056/NEJMoa0908492 19843557
12. Beyond Thailand: Making Sense of a Qualified AIDS Vaccine "Success". J Cohen, Science 2009 326 5953 652 653 10.1126/science.326- 652 19900904
13. HIV vaccine research: the way forward. AS Fauci MI Johnston CW Dieffenbach DR Burton SM Hammer JA Hoxie M Martin J Overbaugh DI Watkins A Mahmoud, Science 2008 321 5888 530 532 10.1126/science.1161000 18653883
14. The immune response to AIDS virus infection: good, bad, or both? S Deeks B Walker, J Clin Invest 2004 113 6 808 810 15067312
15. Correlates of immune protection in HIV-1 infection: what we know, what we don't know, what we should know. G Pantaleo RA Koup, Nat Med 2004 10 806 810 10.1038/nm0804-806 15286782
16. Detection of Human Immunodeficiency Virus Type 1 Envelope Peptide-Stimulated T-helper Cell Responses and Variations in the Corresponding Regions of Viral Isolates among Vertically Infected Children. S Meddows-Taylor MA Papathanasopoulos L Kuhn TM Meyers CT Tiemessen, Virus Genes 2004 28 3 311 318 10.1023/B:VIRU.0000025788.85010.bd 15266112
17. Characterization of a V3 domain-specific neutralizing human monoclonal antibody that preferentially recognizes non-syncytium-inducing human immunodeficiency virus type 1 strains. M Schutten JPM Langedijk AC Andeweg RC Huisman RH Meloen A Osterhaus, J Gen Virol 1995 76 7 1665 1673 10.1099/0022-1317-76-7-1665 9049372
18. Molecular analysis of the same HIV peptide functionally binding to both a class I and a class II MHC molecule. T Takeshita H Takahashi S Kozlowski JD Ahlers CD Pendleton RL Moore Y Nakagawa K Yokomuro BS Fox DH Margulies, The Journal of Immunology 1995 154 4 1973 1986 7530749
19. A chain section containing epitopes for cytotoxic T, B and helper T cells within a highly conserved region found in the human immunodeficiency virus type 1 Gag protein. Y Nakamura M Kameoka M Tobiume M Kaya K Ohki T Yamada K Ikuta, Vaccine 1997 15 5 489 496 10.1016/S0264-410X(96)00224-1 9160516
20. Escape of Human Immunodeficiency Virus from immune control. AJ McMichael RE Phillips, Annu Rev Immunol 1997 15 1 271 296 10.1146/annurev.immunol.15.1.271 9143689
21. A novel HIV T helper epitope-based vaccine elicits cytokine-secreting HIV-specific CD4 T cells in a Phase I clinical trial in HIV-uninfected adults. X Jin MJ Newman S De-Rosa C Cooper E Thomas M Keefer J Fuchs W Blattner BD Livingston DM McKinney, Vaccine 2009 27 7080 7086 10.1016/j.vaccine.2009.09.060 19786145
22. Protection against chronic infection and AIDS by an HIV envelope peptide-cocktail vaccine in a pathogenic SHIV-rhesus model. PN Nehete S Chitta MM Hossain L Hill BJ Bernacky W Baze RB Arlinghaus KJ Sastry, Vaccine 2001 20 5-6 813 825 10.1016/S0264-410X(01)00408-X 11738745
23. Epitope-based vaccines: an update on epitope identification, vaccine design and delivery. A Sette J Fikes, Curr Opin Immunol 2003 15 4 461 470 10.1016/S0952-7915(03)00083-9 12900280
24. Safety and immunogenicity of a CTL multiepitope peptide vaccine for HIV with or without GM-CSF in a phase I trial. P Spearman S Kalams M Elizaga B Metch YL Chiu M Allen KJ Weinhold G Ferrari SD Parker MJ McElrath, Vaccine 2009 27 243 249 18996425
25. Immunology. J Klein V Horejsi, Oxford, UK: Blackwell Science 1997
26. Co-evolution of human immunodeficiency virus and cytotoxic T-lymphocyte responses. P Goulder D Price M Nowak S Rowland-Jones R Phillips A McMichael, Immunol Rev 1997 159 17 29 10.1111/j.1600-065X.1997.tb01004.x 9416500
27. Transfer of HIV-1-specific cytotoxic T lymphocytes to an AIDS patient leads to selection for mutant HIV variants and subsequent disease progression. S Koenig AJ Conley YA Brewah GM Jones S Leath LJ Boots V Davey G Pantaleo JF Demarest C Carter, Nat Med 1995 1 4 330 336 10.1038/nm0495-330 7585062
28. Determinants of human immunodeficiency virus type 1 escape from the primary CD8+ cytotoxic T lymphocyte response. NA Jones X Wei DR Flower M Wong F Michor MS Saag BH Hahn MA Nowak GM Shaw P Borrow, J Exp Med 2004 200 10 1243 1256 10.1084/jem.20040511 15545352
29. Q&A: What do we know about influenza and what can we do about it? PC Doherty SJ Turner, J Biol 2009 8 5 46 10.1186/jbiol147 19519930
30. A Dominant Role for CD8 -T-Lymphocyte Selection in Simian Immunodeficiency Virus Sequence Variation. DH O'Connor AB McDermott KC Krebs EJ Dodds JE Miller EJ Gonzalez TJ Jacoby L Yant H Piontkivska R Pantophlet, J Virol 2004 78 24 14012 14022 10.1128/JVI.78.24.14012-14022.2004 15564508
31. Immune-mediated positive selection drives human immunodeficiency virus type 1 molecular variation and predicts disease duration. HA Ross AG Rodrigo, J Virol 2002 76 22 11715 11720 10.1128/JVI.76.22.11715-11720.2002 12388731
32. CD8 Epitope Escape and Reversion in Acute HCV Infection. J Timm GM Lauer DG Kavanagh I Sheridan AY Kim M Lucas T Pillay K Ouchi LL Reyor JS zur Wiesch, J Exp Med 2004 200 12 1593 1604 10.1084/jem.20041006 15611288
33. T-lymphocyte epitope identification and their use in vaccine development for HIV-1. MJ Newman B Livingston DM McKinney RW Chesnut A Sette TL Subsets-immunology, Front Biosci 2002 7 1503 1515 10.2741/newman 12048179
34. Multiepitopic B-and T-cell responses induced in humans by a human immunodeficiency virus type 1 lipopeptide vaccine. H Gahery-Segard G Pialoux B Charmeteau S Sermet H Poncelet M Raux A Tartar JP Levy H Gras-Masse JG Guillet, J Virol 2000 74 4 1694 1703 10.1128/JVI.74.4.1694-1703.2000 10644339
35. The multi-epitope polypeptide approach in HIV-1 vaccine development. CA Duarte Cano, Genet Anal: Biomol Eng 1999 15 3-5 149 153 10.1016/S1050-3862(99) 00019-4 (Pubitemid 29531538)
36. The Multi-Epitope Approach to Development of HIV Vaccines [abstract]. M Newman B Livingston D McKinney R Chesnut A Sette, AIDS Vaccine 2001 No:35
37. The causes and consequences of HIV evolution. A Rambaut D Posada KA Crandall EC Holmes, Nature Reviews Genetics 2004 5 1 52 61 10.1038/nrg1246 14708016
38. HIV-1 Genetic Diversity and Its Biological Significance. MM Thomson, HIV and the Brain: New Challenges in the Modern Era New York: Humana Press, Paul RH, Sacktor ND, Valcour V, Tashima KT, 2009 267 291
39. High rate of recombination throughout the human immunodeficiency virus type 1 genome. AE Jetzt H Yu GJ Klarmann Y Ron BD Preston JP Dougherty, J Virol 2000 74 3 1234 1240 10.1128/JVI.74.3.1234-1240.2000 10627533
40. Recombination in AIDS viruses. DL Robertson BH Hahn PM Sharp, J Mol Evol 1995 40 3 249 259 10.1007/BF00163230 7723052
41. Human immunodeficiency virus type 1 recombination: rate, fidelity, and putative hot spots. J Zhuang AE Jetzt G Sun H Yu G Klarmann Y Ron BD Preston JP Dougherty, J Virol 2002 76 22 11273 11282 10.1128/JVI.76.22.11273-11282.2002 12388687
42. Simultaneous positive and purifying selection on overlapping reading frames of the tat and vpr genes of simian immunodeficiency virus. AL Hughes K Westover J da Silva DH O'Connor DI Watkins, Journal of virology 2001 75 17 7966 72 10.1128/JVI.75.17.7966-7972.2001 11483741
43. Evolutionary and immunological implications of contemporary HIV-1 variation. B Korber B Gaschen K Yusim R Thakallapally C Kesmir V Detours, Br Med Bull 2001 58 1 19 42 10.1093/bmb/58.1.19 11714622
44. Discovery of novel targets for multi-epitope vaccines: Screening of HIV-1 genomes using association rule mining. S Paul H Piontkivska, Retrovirology 2009 6 62 10.1186/1742-4690-6-62 19580659
45. Development of artificial vaccines against HIV using defined epitopes. J Berzofsky, The FASEB Journal 1991 5 10 2412 2418 1712327
46. An HIV vaccine-evolving concepts. MI Johnston AS Fauci, N Engl J Med 2007 356 20 2073 2081 10.1056/NEJMra066267 17507706
47. Studies on GM-CSF DNA as an adjuvant for neutralizing Ab elicited by a DNA/MVA immunodeficiency virus vaccine. HL Robinson DC Montefiori F Villinger JE Robinson S Sharma LS Wyatt PL Earl HM McClure B Moss RR Amara, Virology 2006 352 2 285 294 10.1016/j.virol.2006.02.011 16740288
48. Helper-cytotoxic T lymphocyte (CTL) determinant linkage required for priming of anti-HIV CD8 CTL in vivo with peptide vaccine constructs. M Shirai CD Pendleton J Ahlers T Takeshita M Newman JA Berzofsky, The Journal of Immunology 1994 152 2 549 556 8283036
49. A Novel Liposome-Based Adjuvant CAF01 for Induction of CD8 Cytotoxic T-Lymphocytes (CTL) to HIV-1 Minimal CTL Peptides in HLA-A* 0201 Transgenic Mice. GJ Gram I Karlsson EM Agger P Andersen A Fomsgaard, PLoS One 2009 4 9 6950 10.1371/journal.pone.0006950 19759892
50. Rapid reversion of sequence polymorphisms dominates early human immunodeficiency virus type 1 evolution. B Li AD Gladden M Altfeld JM Kaldor DA Cooper AD Kelleher TM Allen, J Virol 2007 81 1 193 201 10.1128/JVI.01231-06 17065207
51. HIV-1 subtype and circulating recombinant form (CRF) reference sequences, 2005. T Leitner B Korber M Daniels C Calef B Foley, HIV sequence compendium 2005 2005 41 48
52. Reference sequences representing the principle genetic diversity of HIV-1 in the Pandemic. JK Carr BT Foley T Leitner M Salminen B Korber F McCutchan, Human retroviruses and AIDS 1998 Los Alamos, NM: Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Korber B, Kuiken CL, Foley B, Hahn B, McCutchan F, Mellors JW, Sodroski J, 1998 III 10 19
53. HIV-1 nomenclature proposal. DL Robertson JP Anderson JA Bradac JK Carr B Foley RK Funkhouser F Gao BH Hahn C Kuiken GH Learn T Leitner F McCutchan S Osmanov M Peeters D Pieniazek ML Kalish M Salminen PM Sharp S Wolinsky B Korber, Human Retroviruses and AIDS 1999 Los Alamos, NM: Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Kuiken CL, Foley B, Hahn B, Korber B, McCutchan F, Marx PA, Mellors JW, Mullins JI, Sodroski J, Wolinsky S, 1999 492 505
54. HIV sequence databases. C Kuiken B Korber RW Shafer, AIDS reviews 2003 5 1 52 61 12875108
55. Using databases and data mining in vaccinology. MN Davies P Guan MJ Blythe J Salomon CP Toseland C Hattotuwagama V Walshe IA Doytchinova DR Flower, Expert Opinion on Drug Discovery 2007 2 1 19 35 10.1517/17460441.2.1.19 (Pubitemid 47078696)
56. Identification of HIV-derived, HLA class I restricted CTL epitopes: insights into TCR repertoire, CTL escape and viral fitness. N Frahm C Linde C Brander, HIV molecular immunology 2006 2007 3 28
57. The implications of patterns in HIV diversity for neutralizing antibody induction and susceptibility. B Korber S Gnanakaran, Current Opinion in HIV and AIDS 2009 4 5 408 417 10.1097/COH.0b013e32832f129e 20048705
58. Structure-function relationships of HIV-1 envelope sequence-variable regions refocus vaccine design. S Zolla-Pazner T Cardozo, Nature Reviews Immunology 2010 10 7 527 535 10.1038/nri2801 20577269
59. Immune epitope mapping in the post-genomic era: lessons for vaccine development. A Sette B Peters, Curr Opin Immunol 2007 19 1 106 110 10.1016/j.coi.2006.11.002 17113275
60. T-cell epitope mapping. L Malherbe, Annals of Allergy, Asthma and Immunology 2009 103 1 76 79 10.1016/S1081-1206(10)60147-0
61. Generation of human monoclonal antibodies to human immunodeficiency virus. MK Gorny V Gianakakos S Sharpe S Zolla-Pazner, Proceedings of the National Academy of Sciences 1989 86 5 1624 1628 10.1073/pnas.86.5.1624 (Pubitemid 19078955)
62. Immunodominant epitope regions of HIV-1 reverse transcriptase: correlations with HIV-1 serum IgG inhibitory to polymerase activity and with disease progression. B Grimison J Laurence, JAIDS J Acquired Immune Defic Syndromes 1995 9 1 58 68
63. Correlating low-similarity peptide sequences and HIV B-cell epitopes. D Kanduc R Serpico A Lucchese Y Shoenfeld, Autoimmun Rev 2008 7 4 291 296 10.1016/j.autrev.2007.11.001 18295732 (Pubitemid 351284547)
64. Identification of immunodominant epitopes in inactivated Tat-vaccinated healthy and HIV-1-infected volunteers. DM Noonan A Gringeri R Meazza O Rosso S Mazza M Muça-Perja H Le Buanec RS Accolla A Albini S Ferrini, JAIDS J Acquired Immune Defic Syndromes 2003 33 1 47 55
65. Expression of a novel Nef epitope on the surface of HIV type 1-infected cells. T Yamada A Iwamoto, AIDS Res Hum Retroviruses 1999 15 11 1001 1009 10.1089/088922299310511 10445812
66. IH Witten E Frank, Data mining: practical machine learning tools and techniques San Francisco: Morgan Kaufmann 2005
67. Mining association rules between sets of items in large databases. R Agrawal T Imieliski A Swami, Proceedings of the ACM SIGMOD International Conference on Management of Data: 26-28 May 1993; Washington, DC ACM Press, Peter Buneman, Sushil Jajodia, 1993 207 216 full-text
68. An association-based clustering approach to order batching considering customer demand patterns. MC Chen HP Wu, Omega 2005 33 4 333 343 10.1016/j.omega.2004.05.003 (Pubitemid 40131306)
69. Using associative classification for predicting HIV-1 drug resistance. A Srisawat B Kijsirikul, Proceedings of the Fourth International Conference on Hybrid Intelligent Systems: 5-8 December 2004; Kitakyushu, Japan. IEEE Computer Society 2005 280 284
70. Modified Association Rule Mining Approach for the MHC-Peptide Binding Problem. GG Yardmc A Küçükural Y Saygn U Sezerman, Lecture Notes in Computer Science 2006 4263 165 173 full-text
71. Microbial genotype-phenotype mapping by class association rule mining. M Tamura P D'haeseleer, Bioinformatics 2008 24 13 1523 1529 10.1093/ bioinformatics/btn210 18467347
72. Data mining in bioinformatics using Weka. E Frank M Hall L Trigg G Holmes IH Witten, Bioinformatics 2004 20 15 2479 2481 10.1093/bioinformatics/bth261 15073010
73. Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. M Nei T Gojobori, Mol Biol Evol 1986 3 5 418 426 3444411
74. M Nei S Kumar, Molecular evolution and phylogenetics New York: Oxford University Press 2000
75. MEGA4: molecular evolutionary genetics analysis (MEGA) software version 4.0. K Tamura J Dudley M Nei S Kumar, Mol Biol Evol 2007 24 8 1596 1599 10.1093/molbev/msm092 17488738
76. Diversity considerations in HIV-1 vaccine selection. B Gaschen J Taylor K Yusim B Foley F Gao D Lang V Novitsky B Haynes BH Hahn T Bhattacharya, Science 2002 296 5577 2354 2360 10.1126/science.1070441 12089434
77. Origin of HIV-1 in Pan troglodytes troglodytes. F Gao E Bailes DL Robertson Y Chen CM Rodenburg SF Michael LB Cummins LO Arthur M Peeters GM Shaw, Nature 1999 397 6718 436 441 10.1038/17130 9989410
78. Between-Host Evolution of Cytotoxic T-Lymphocyte Epitopes in Human Immunodeficiency Virus Type 1: an Approach Based on Phylogenetically Independent Comparisons. H Piontkivska AL Hughes, J Virol 2004 78 21 11758 11765 10.1128/JVI.78.21.11758-11765.2004 15479817
79. Patterns of sequence evolution at epitopes for host antibodies and cytotoxic T-lymphocytes in human immunodeficiency virus type 1. H Piontkivska AL Hughes, Virus Res 2006 116 1-2 98 105 10.1016/j.virusres.2005.09.001 16214253
80. Isolation and partial characterization of an unusual human immunodeficiency retrovirus from two persons of west-central African origin. R De Leys B Vanderborght M Vanden Haesevelde L Heyndrickx A Van Geel C Wauters R Bernaerts E Saman P Nijs B Willems, J Virol 1990 64 3 1207 1216 2304140
81. The origins of acquired immune deficiency syndrome viruses: where and when? PM Sharp E Bailes RR Chaudhuri CM Rodenburg MO Santiago BH Hahn, Philosophical Transactions: Biological Sciences 2001 356 867 876 10.1098/rstb.2001.0863 (Pubitemid 32614662)
82. Identification of a new human immunodeficiency virus type 1 distinct from group M and group O. F Simon P Mauclère P Roques I Loussert-Ajaka MC Müller-Trutwin S Saragosti MC Georges-Courbot F Barré-Sinoussi F Brun-Vézinet, Nat Med 1998 4 9 1032 1037 10.1038/2017 9734396 (Pubitemid 28417335)
83. Architecture and secondary structure of an entire HIV-1 RNA genome. JM Watts KK Dang RJ Gorelick CW Leonard JW Bess Jr R Swanstrom CL Burch KM Weeks, Nature 2009 460 7256 711 716 10.1038/nature08237 19661910
84. A systematic bioinformatics approach for selection of epitope-based vaccine targets. AM Khan O Miotto A Heiny J Salmon K Srinivasan EJM Nascimento ETA Marques V Brusic TW Tan JT August, Cell Immunol 2006 244 2 141 147 10.1016/j.cellimm.2007.02.005 17434154
85. An introduction to epitope prediction methods and software. X Yang X Yu, Rev Med Virol 2008 19 77 96 10.1002/rmv.602
86. The development of multi-epitope vaccines: epitope identification, vaccine design and clinical evaluation. A Sette B Livingston D McKinney E Appella J Fikes J Sidney M Newman R Chesnut, Biologicals 2001 29 3-4 271 276 10.1006/biol.2001.0297 11851327
87. Prediction of Immunogenicity of Therapeutic Proteins: Validity of Computational Tools. CJ Bryson TD Jones MP Baker, BioDrugs 2010 24 1 1 8 10.2165/11318560-000000000-00000 20055528
88. Hypervariable epitope constructs as a means of accounting for epitope variability. DE Anderson A Malley E Benjamini MB Gardner JV Torres, Vaccine 1994 12 8 736 740 10.1016/0264-410X(94)90225-9 7522382
89. Vaccination with CTL epitopes that escape: an alternative approach to HIV vaccine development? D O'Connor T Allen DI Watkins, Immunol Lett 2001 79 1-2 77 84 10.1016/S0165-2478(01)00268-1 11595292
90. Immunogenicity of a vaccine preparation representing the variable regions of the HIV type 1 envelope glycoprotein. MP Carlos DE Anderson MB Gardner JV Torres, AIDS Res Hum Retroviruses 2000 16 2 153 161 10.1089/088922200309494 10659054
91. Induction of broad cross-subtype-specific HIV-1 immune responses by a novel multivalent HIV-1 peptide vaccine in cynomolgus macaques. A Azizi DE Anderson JV Torres A Ogrel M Ghorbani C Soare P Sandstrom J Fournier F Diaz-Mitoma, The Journal of Immunology 2008 180 4 2174 2186 18250424
92. The rationale behind a vaccine based on multiple HIV antigens. E Rollman A Bråve A Boberg L Gudmundsdotter G Engström M Isaguliants K Ljungberg B Lundgren P Blomberg J Hinkula, Microb Infect 2005 7 14 1414 1423
93. Immunodominant HIV-1 CD4 T cell epitopes in chronic untreated clade C HIV-1 infection. D Ramduth CL Day CF Thobakgale NP Mkhwanazi C De Pierres S Reddy M Van Der Stok Z Mncube K Nair ES Moodley, PLoS One 2009 4 4 5013 10.1371/journal.pone.0005013 19352428
94. A Vaccine Encoding Conserved Promiscuous HIV CD4 Epitopes Induces Broad T Cell Responses in Mice Transgenic to Multiple Common HLA Class II Molecules. S Ribeiro D Rosa S Fonseca E Mairena E Postál MA Ostrowski, PLoS ONE 2010 5 6 11072 10.1371/journal.pone.0011072 20552033
95. Extensive HLA class I allele promiscuity among viral CTL epitopes. N Frahm K Yusim TJ Suscovich S Adams J Sidney P Hraber HS Hewitt CH Linde DG Kavanagh T Woodberry LM Henry K Faircloth J Listgarten C Kadie N Jojic K Sango NV Brown E Pae MT Zaman F Bihl A Khatri M John S Mallal FM Marincola BD Walker A Sette D Heckerman BT Korber C Brander, Eur J Immunol 2007 37 9 2419 2433 10.1002/eji.200737365 17705138
96. Comprehensive analysis of human immunodeficiency virus type 1-specific CD4 responses reveals marked immunodominance of gag and nef and the presence of broadly recognized peptides. DE Kaufmann PM Bailey J Sidney B Wagner PJ Norris MN Johnston LA Cosimi MM Addo M Lichterfeld M Altfeld, J Virol 2004 78 9 4463 4477 10.1128/JVI.78.9.4463-4477.2004 15078927
97. Structural and functional constraints limit options for cytotoxic T-lymphocyte escape in the immunodominant HLA-B27-restricted epitope in human immunodeficiency virus type 1 capsid. A Schneidewind MA Brockman J Sidney YE Wang H Chen TJ Suscovich B Li RI Adam RL Allgaier BR Mothe, J Virol 2008 82 11 5594 5605 10.1128/JVI.02356-07 18385228
98. Protective HLA Class I Alleles That Restrict Acute-Phase CD8 T-Cell Responses Are Associated with Viral Escape Mutations Located in Highly Conserved Regions of Human Immunodeficiency Virus Type 1. YE Wang B Li JM Carlson H Streeck AD Gladden R Goodman A Schneidewind KA Power I Toth N Frahm, J Virol 2009 83 4 1845 1855 10.1128/JVI.01061-08 19036810
99. Structure of the amino-terminal core domain of the HIV-1 capsid protein. RK Gitti BM Lee J Walker MF Summers S Yoo WI Sundquist, Science 1996 273 5272 231 235 10.1126/science.273.5272.231 8662505
100. Image reconstructions of helical assemblies of the HIV-1 CA protein. S Li CP Hill WI Sundquist JT Finch, Nature 2000 407 6802 409 413 10.1038/35030177 11014200
101. X-ray structures of the hexameric building block of the HIV capsid. O Pornillos BK Ganser-Pornillos BN Kelly Y Hua FG Whitby CD Stout WI Sundquist CP Hill M Yeager, Cell 2009 137 7 1282 1292 10.1016/j.cell.2009.04.063 19523676
102. Dissecting the Protein-RNA and RNA-RNA Interactions in the Nucleocapsid-mediated Dimerization and Isomerization of HIV-1 Stemloop 1. NA Hagan D Fabris, J Mol Biol 2007 365 2 396 410 10.1016/j.jmb.2006.09.081 17070549
103. Cytokine-in-adjuvant steering of the immune response phenotype to HIV-1 vaccine constructs: granulocyte-macrophage colony-stimulating factor and TNF-alpha synergize with IL-12 to enhance induction of cytotoxic T lymphocytes. JD Ahlers N Dunlop DW Alling PL Nara JA Berzofsky, The Journal of Immunology 1997 158 8 3947 3958 9103465
104. OA04-01. Safety and immunogenicity of LIPO-5, a HIV-1 lipopeptide vaccine: results of ANRS VAC18, a phase 2, randomized, double-blind, placebo-controlled trial. D Salmon-Ceron C Durier C Desaint, Retrovirology 2009 6 Suppl 3 25 10.1186/1742-4690-6-S3-O25
105. T-Cell Epitope Prediction: Rescaling Can Mask Biological Variation between MHC Molecules. A MacNamara U Kadolsky CRM Bangham B Asquith, PLoS Computational Biology 2009 5 3 1000327 10.1371/journal.pcbi.1000327 19300484
106. Prediction of Linear B-cell Epitopes. U Reimer, Methods in Molecular Biology Totowa, USA: Humama Press, Reineke U, Schutkowski M, 2009 524 335 344 full-text 19377956
107. Development of an epitope conservancy analysis tool to facilitate the design of epitope-based diagnostics and vaccines. HH Bui J Sidney W Li N Fusseder A Sette, BMC Bioinformatics 2007 8 361 10.1186/1471-2105-8-361 17897458
108. Identification of highly immunodominant regions in HIV by comprehensive CTL screening of ethnically diverse populations. N Frahm C Adams R Draenert M Feeney K Sango NV Brown D SenGupta T Simonis F Marincola A Wurcel, J Virol 2004 78 2187 2200 10.1128/JVI.78.5.2187-2200.2004 14963115
109. Unlocking the potential of the human genome with RNA interference. GJ Hannon JJ Rossi, Nature 2004 431 7006 371 378 10.1038/nature02870 15372045
110. Dimerization inhibitors of HIV-1 reverse transcriptase, protease and integrase: A single mode of inhibition for the three HIV enzymes? MJ Camarasa S Velzquez A San-Félix MJ Pérez-Pérez F Gago, Antiviral Res 2006 71 2-3 260 267 10.1016/j.antiviral.2006.05.021 16872687
111. Nef binds p6* in GagPol during replication of human immunodeficiency virus type 1. LJ Costa YH Zheng J Sabotic J Mak OT Fackler BM Peterlin, J Virol 2004 78 10 5311 5323 10.1128/JVI.78.10.5311-5323.2004 15137387
112. Potent nonnucleoside reverse transcriptase inhibitors target HIV-1 Gag-Pol. A Figueiredo KL Moore J Mak N Sluis-Cremer MP de Bethune G Tachedjian, PLoS Pathog 2006 2 11 119 10.1371/journal.ppat.0020119 17096588
113. Quantitative analysis of the interactions between HIV-1 integrase and retroviral reverse transcriptases. A Herschhorn I Oz-Gleenberg A Hizi, Biochem J 2008 412 163 170 10.1042/BJ20071279 18260826
114. Protein-protein interactions as targets for antiviral chemotherapy. A Loregian HS Marsden G Palu, Rev Med Virol 2002 12 4 239 262 10.1002/rmv.356 12125015
115. Interaction between HIV-1 Rev and integrase proteins: a basis for the development of anti-HIV peptides. J Rosenbluh Z Hayouka S Loya A Levin A Armon-Omer E Britan A Hizi M Kotler A Friedler A Loyter, J Biol Chem 2007 282 21 15743 15753 10.1074/jbc.M609864200 17403681
116. Domains upstream of the protease (PR) in human immunodeficiency virus type 1 Gag-Pol influence PR autoprocessing. G Zybarth C Carter, The Journal of Virology 1995 69 6 3878 3884