Human immunodeficiency virus proteins mimic human T cell receptors inducing cross-reactive antibodies

International Journal of Molecular Sciences

Volumn 18, Issue 10, 2017, Pages

  Root Bernstein, Robert ^a  

^a MICHIGAN STATE UNIVERSITY   (United States)

Author keywords

Acquired immunodeficiency syndrome; Antigenic mimicry; Autoholoimmunity; Autoimmunity; Holoimmunity; Lymphocytotoxic autoantibodies; Microbiome; Tolerance

Indexed keywords

CROSS REACTING ANTIBODY; HUMAN IMMUNODEFICIENCY VIRUS PROTEIN; T LYMPHOCYTE RECEPTOR; LYMPHOCYTE ANTIGEN RECEPTOR;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; AMINO ACID SEQUENCE; ARTICLE; BACTERIAL INFECTION; CONTROLLED STUDY; CYTOMEGALOVIRUS; DISEASE ASSOCIATION; ENZYME LINKED IMMUNOSORBENT ASSAY; HEPATITIS C VIRUS; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; MOLECULAR MIMICRY; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PREVALENCE; PROTEOMICS; PROTOZOAL INFECTION; ANIMAL; AUTOIMMUNITY; CHEMISTRY; CROSS REACTION; IMMUNOLOGY; MICROFLORA; VIROLOGY;

ACQUIRED IMMUNODEFICIENCY SYNDROME; ANIMALS; AUTOIMMUNITY; CROSS REACTIONS; HIV; HUMAN IMMUNODEFICIENCY VIRUS PROTEINS; HUMANS; MICROBIOTA; MOLECULAR MIMICRY; PROTEOMICS; RECEPTORS, ANTIGEN, T-CELL;

EID: 85030713139     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms18102091     Document Type: Article

References (111)

1. Margulis, L.; Fester, R. Symbiosis as a Source of Evolutionary Innovation. Cambridge, MA: MIT Press, 1991.
2. Mindell, D.P. Phylogenetic consequences of symbioses: Eukarya and Eubacteria are not monophyletic taxa. BioSystems 1992, 27, 53-62.
3. Root-Bernstein, R.S. Autoimmunity and the microbiome: T-cell receptor mimicry of “self” and microbial antigens mediates self tolerance in holobionts. BioEssays 2016, 38, 1068-1083, doi:10.1002/bies.201600083.
4. De Groot, A.S.; Moise, L.; Liu, R.; Gutierrez, A.H.; Tassone, R.; Bailey-Kellogg, C.; Martin, W. Immune camouflage: Relevance to vaccines and human immunology. Hum. Vaccin. Immunother. 2014, 10, 3570-3575, doi:10.4161/hv.36134.
5. Moise, L.; Terry, F.; Gutierrez, A.H.; Tassone, R.; Losikoff, P.; Gregory, S.H.; Bailey-Kellogg, C.; Martin, W.D.; de Groot, A.S. Smarter vaccine design will circumvent regulatory T cell-mediated evasion in chronic HIV and HCV infection. Front. Microbiol. 2014, 5, 502, doi:10.3389/fmicb.2014.00502
6. Moise, L.; Beseme, S.; Tassone, R.; Liu, R.; Kibria, F.; Terry, F.; Martin, W.; de Groot, A.S. T cell epitope redundancy: Cross-conservation of the TCR face between pathogens and self and its implications for vaccines and autoimmunity. Expert Rev. Vaccines 2016, 15, 607-617, doi:10.1586/14760584.2016.1123098.
7. Yan, N.; Lieberman, J. Gaining a foothold: How HIV avoids innate immune recognition. Curr. Opin. Immunol. 2011, 23, 21-28, doi:10.1016/j.coi.2010.11.004.
8. Rasaiyaah, J.; Tan, C.P.; Fletcher, A.J.; Price, A.J.; Blondeau, C.; Hilditch, L.; Jacques, D.A.; Selwood, D.L.; James, L.C.; Noursadeghi,M.; et al. HIV-1 evades innate immune recognition through specific cofactor recruitment. Nature 2013, 503, 402-5, doi:10.1038/nature12769.
9. Guha, D.; Ayyavoo, V. Innate immune evasion strategies by Human Immunodeficiency Virus Type 1. ISRN AIDS 2013, 954806, doi:10.1155/2013/954806.
10. Via, C.S.; Shearer, G.M. Autoimmunity and the acquired immune deficiency syndrome. Curr. Opin. Immunol. 1989, 1, 753-756.
11. Malatzky-Goshen, E.; Shoenfeld, Y. AIDS and autoimmunity. Autoimmunity 1989, 3, 201-212.
12. Morrow, W.J.; Isenberg, D.A.; Sobol, R.E.; Stricker, R.B.; Kieber-Emmons, T. AIDS virus infection and autoimmunity: A perspective of the clinical, immunological, and molecular origins of the autoallergic pathologies associated with HIV disease. Clin. Immunol. Immunopathol. 1991, 58, 163-80.
13. Bjork, R.L. HIV-1: Seven facets of functional molecular mimicry. Immunol. Lett. 1991, 28, 91-96.
14. Root-Bernstein, R.S.; Hobbs, S.H. Homologies between mycoplasma adhesion peptide, CD4, and class II MHC proteins: A possible mechanism for HIV mycoplasma synergism in AIDS. Res. Immunol. 1992, 142, 519-523.
15. Root-Bernstein, R.S. Rethinking AIDS. The Tragic Cost of Premature Concensus. New York: Free Press, 1993.
16. Russo, S.; Lopalco, L. Is autoimmunity a component of natural immunity to HIV? Curr. HIV Res. 2006, 4, 177-190.
17. Huang, Y.M.; Hong, X.Z.; Xu, J.H.; Luo, J.X.; Mo, H.Y.; Zhao, H.L. Autoimmunity and dysmetabolism of human acquired immunodeficiency syndrome. Immunol. Res. 2016, 64, 641-652, doi:10.1007/s12026015-8767-5.
18. Beretta, A.; Grassi, F.; Pelagi, M.; Clivio, A.; Parravicini, C.; Giovinazzo, G.; Andronico, F.; Lopalco, L.; Verani, P.; Buttò, S. HIV env glycoprotein shares a cross-reacting epitope with a surface protein present on activated human monocytes and involved in antigen presentation. Eur. J. Immunol. 1987, 17, 1793-1798.
19. Golding, H.; Robey, F.A.; Gates, F.T.; Linder, W.; Beining, P.R.; Hoffman, T.; Golding, B. Identification of homologous regions in human immunodeficiency virus I gp41 and human MHC class II β 1 domain. I. Monoclonal antibodies against the gp41-derived peptide and patients’ sera react with native HLA class II antigens, suggesting a role for autoimmunity in the pathogenesis of acquired immune deficiency syndrome. J. Exp. Med. 1988, 167, 914-923.
20. Golding, H.; Shearer, G.M.; Hillman, K.; Lucas, P.; Manischewitz, J.; Zajac, R.A.; Clerici, M.; Gress, R.E.; Boswell, R.N.; Golding, B. Common epitope in human immunodeficiency virus (HIV) I-GP41 and HLA class II elicits immunosuppressive autoantibodies capable of contributing to immune dysfunction in HIV I-infected individuals. J. Clin. Invest. 1989, 83, 1430-1435.
21. Grassi, F.; Meneveri, R.; Gullberg, M.; Lopalco, L.; Rossi, G.B.; Lanza, P.; De Santis, C.; Brattsand, G.; Buttò, S.; Ginelli, E. Human immunodeficiency virus type 1 gp120 mimics a hidden monomorphic epitope borne by class I major histocompatibility complex heavy chains. J. Exp. Med. 1991, 174, 53-62.
22. Lopalco, L.; de Santis, C.; Meneveri, R.; Longhi, R.; Ginelli, E.; Grassi, F.; Siccardi, A.G.; Beretta, A. Human immunodeficiency virus type 1 gp120 C5 region mimics the HLA class I alpha 1 peptide-binding domain. Eur. J. Immunol. 1993, 23, 2016-2021.
23. Powell, P.D.; DeMartini, J.C.; Azari, P.; Stargell, L.A.; Cordain, L.; Tucker, A. Evolutionary stable strategy:a test for theories of retroviral pathology which are based upon the concept of molecular mimicry. J. Theor. Biol. 2000, 202, 213-229.
24. Root-Bernstein, R.S.; Dewitt, S.H. CD4 similarity to proteins of infectious agents in AIDS and their role in autoimmunity. Med. Hypoth. 1994, 43, 361-371.
25. Root-Bernstein, R.S. Preliminary evidence of idiotype-antiidiotype immune complexes cross reactive with lymphocyte antigens in AIDS and lupus. Med. Hypoth. 1995, 44, 20-27.
26. Root-Bernstein, R.S. Antigenic complementarity between HIV and other AIDS-associated infections results in idiotype-antiidiotype antibody complexes that cross-react with lymphocyte proteins. Vaccine 2005, 23, 2160-2163.
27. Root-Bernstein, R.S.; Rallo, A. Antigenic complementarity resulting in idiotype-antiidiotype immune complexes: Possible contributor to AIDS pathogenesis and autoimmunity. Autoimmunity 2004, 37, 203-210.
28. Root-Bernstein, R.S. Antigenic complementarity among AIDS-associated infectious agents and molecular mimicry of lympohocyte proteins as inducers of lymphocytotoxic antibodies and circulating immune complexes. J. Clin. Virol. 2004, 31, 16-25, doi:10.1016/j.jcv.2004.09.009.
29. Trujillo, J.R.; Rogers, R.A.; Brain, J.D. Shared antigenic epitopes on the V3 loop of HIV-1 gp120 and proteins on activated human T cells. Virology 1998, 246, 53-62.
30. Lake, D.F.; Schlute, S.F.; Wang, E.; Bernstein, R.M.; Edmundson, A.B.; Marchalonis, J.J. Autoantibodies to the α/β T-cell receptors in human immunodeficiency virus infection: dysregulation and mimicry. Proc. Natl. Acad. Sci. USA 1994, 91, 10849-10853.
31. Marchalonis, J.J.; Lake, D.F.; Schluter, S.F.; Dehghanpisheh, K.; Watson, R.R.; Ampe,l N.M.; Galgiani, J.N. Autoantibodies against peptide-defined epitopes of T-cell receptors in retrovirally infected humans and mice. Adv. Exp. Med. Biol. 1995, 383, 211-222.
32. Sheikh, J.; Ongradi, J.; Austen, B.; Dalgleish, A. The potential importance of MHC mimicry by HIV in the pathogenesis of AIDS. Biochem. Soc. Trans. 1995, 23, 471-479.
33. Süsal, C.; Kröpelin, M.; Daniel, V.; Opelz, G. Molecular mimicry between HIV-1 and antigen receptor molecules: A clue to the pathogenesis of AIDS. Vox Sang. 1993, 65, 10-17.
34. Dalgleish, A.G. Autoimmune mechanisms of depletion of CD4 cells in HIV infection. Br. J. Haematol. 1995, 91, 525-534.
35. Chen, Y.H.; Xiao, Y.; Dierich, M.P. HIV-1 gp41 and type I interferon: Sequence homology and biological as well as clinical implications. Immunol. Res. 2000, 22, 61-66.
36. Serres, P.F. AIDS: An immune response against the immune system. Role of a precise tridimensional molecular mimicry. J. Autoimmun. 2001, 16, 287-291.
37. Sanhadji, K.; Tardy, J.C.; Touraine, J.L. HIV-1 infection: Functional competition between gp41 and interleukin-2. C. R. Biol. 2010, 333, 608-612, doi:10.1016/j.crvi.2009.01.009.
38. Su, G.; Min, W.; Taylor, E.W. An HIV-1 encoded peptide mimics the DNA binding loop of NF-κB and binds thioredoxin with high affinity. Mutat. Res. 2005, 579, 133-148.
39. Bettaieb, A.; Fromont, P.; Louache, F.; Oksenhendler, E.; Vainchenker, W.; \Duédari, N.; Bierling, P. Presence of cross-reactive antibody between human immunodeficiency virus (HIV) and platelet glycoproteins in HIV-related immune thrombocytopenic purpura. Blood 1992, 80,162-169.
40. Dominguez, V.; Gevorkian, G.; Govezensky, T.; Rodriguez, H.; Viveros, M.; Cocho, G.; Macotela, Y.; Masso, F.; Pacheco, M.; Estrada, J.L.; et al. Antigenic homology of HIV-1 GP41 and human platelet glycoprotein GPIIIa (integrin beta3). J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 1998, 17, 385-390.
41. Tishkoff, G.H.; Hunt, L.T. Unexpected molecular mimicry among peptides MHC class II, blood-clotting factor X, and HIV-1 envelope glycoprotein GP120. Thromb. Res. 2000, 98, 343-346.
42. Tsiakalos, A.; Routsias, J.G.; Kordossis, T.; Moutsopoulos, H.M.; Tzioufas, A.G.; Sipsas, N.V. Fine epitope specificity of anti-erythropoietin antibodies reveals molecular mimicry with HIV-1 p17 protein: A pathogenetic mechanism for HIV-1-related anemia. J. Infect. Dis. 2011, 204, 902-911, doi:10.1093/infdis/jir433.
43. Li, Z.; Nardi, M.A.; Karpatkin, S. Role of molecular mimicry to HIV-1 peptides in HIV-1-related immunologic thrombocytopenia. Blood 2005, 106, 572-576.
44. Pintér, C.; Siccardi, A.G.; Lopalco, L.; Longhi, R.; Clivio, A. HIV glycoprotein 41 and complement factor H interact with each other and share functional as well as antigenic homology. AIDS Res. Hum. Retroviruses 1995, 11, 971-980.
45. Wiwanitkit, V. Structural homology of HIV-1 GP41 and human platelet glycoprotein GPIIIa. Blood Coagul. Fibrinolysis 2008, 19, 739-740, doi:10.1097/MBC.0b013e32830b14cb.
46. Witte, V.; Laffert, B.; Rosorius, O.; Lischka, P.; Blume, K.; Galler, G.; Stilper, A.; Willbold, D.; D’Aloja, P.; Sixt, M.; et al. HIV-1 Nef mimics an integrin receptor signal that recruits the polycomb group protein Eed to the plasma membrane. Mol. Cell. 2004, 13, 179-190.
47. Pornillos, O.; Higginson, D.S.; Stray, K.M.; Fisher, R.D.; Garrus, J.E.; Payne, M.; He, G.P.; Wang, H.E.; Morham, S.G.; Sundquist, W.I. HIV Gag mimics the Tsg101-recruiting activity of the human Hrs protein. J. Cell Biol. 2003, 162, 425-434.
48. Spehar, T.; Strand, M. Cross-reactivity of anti-human immunodeficiency virus type 1 gp41 antibodies with human astrocytes and astrocytoma cell lines. J. Virol. 1994, 68, 6262-6269.
49. Spehar, T.; Strand, M. Molecular mimicry between HIV-1 gp41 and an astrocyte isoform of α-actinin. J. Neurovirol. 1995, 1, 381-390.
50. Yamada, M.; Zurbriggen, A.; Oldstone, M.B.; Fujinami, R.S. Common immunologic determinant between human immunodeficiency virus type 1 gp41 and astrocytes. J. Virol. 1991, 65, 1370-1376.
51. Trujillo, J.R.; McLane, M.F.; Lee, T.H.; Essex, M. Molecular mimicry between the human immunodeficiency virus type 1 gp120 V3 loop and human brain proteins. J. Virol. 1993, 67, 7711-7715.
52. Eddleston, M.; de la Torre, J.C.; Xu, J.Y.; Dorfman, N.; Notkins, A.; Zolla-Pazner, S.; Oldstone, M.B. Molecular mimicry accompanying HIV-1 infection: Human monoclonal antibodies that bind to gp41 and to astrocytes. AIDS Res. Hum. Retroviruses 1993, 9, 939-944.
53. Atassi, H.; Atassi, M.Z. HIV envelope proteinis recognized as an alloantigen by human DR-specific alloreactive T cells. Hum. Immunol. 1992, 34, 31-38.
54. Nikolich-Zugich, J.; Slifka, M.K.; Messaoudi, I. The many important facets of T-cell repertoire diversity. Nat. Rev. Immunol. 2004, 4, 123-132, doi:10.1038/nri1292.
55. Berson, S. A.; Yalow, R. S. Quantitative aspects of the reaction between insulin and insulin-binding antibody. J. Clin. Invest. 1959, 38, 1996-2016, doi:10.1172/JCI103979.
56. Burch, H. B.; Clement, S.; Sokol, M. S.; Landry, F. Reactive hypoglycemic coma due to insulin autoimmune syndrome: case report and literature review. Am. J. Med. 1992, 92, 681-685, doi:10.1016/0002-9343(92)90787-C.
57. Suzuki, T.; Nishii, N.; Takashima, S.; Matsubara, T.; Iwasawa, A.; Takeuchi, H.; Tahara, K.; Hachisu, T.; Kitagawa, H. Ligand-binding characteristics of feline insulin-binding immunoglobulin G. J. Vet. Med. Sci. 2015, 77, 1379-1383, doi:10.1292/jvms.15-0131.
58. Lin, W.L.; Fincke, J.E.; Sharer, L.R.; Monos, D.S.; Lu, S.; Gaughan, J.; Platsoucas, C.D.; Oleszak, E.L. Oligoclonal T cells are infiltrating the brains of children with AIDS: Sequence analysis reveals high proportions of identical β-chain T-cell receptor transcripts. Clin. Exp. Immunol. 2005, 338-356.
59. Norley, S.; Kurth, R. The role of the immune response during SIVagm infection of the African green monkey natural host. Front. Biosci. 2004, 9, 550-64.
60. Ansari, A.A. Autoimmunity, anergy, lentiviral immunity and disease. Autoimmun. Rev. 2004, 3, 530-540.
61. Lucchese, G.; Stufano, A.; Calabro, M.; Kanduc, D. Charting the peptide crossreactome between HIV-1 and the human proteome. Front. Biosci. 2011, 3, 1385-4000.
62. Venturi, V.; Price, D.A.; Douek, D.C.; Davenport, M.P. The molecular basis for public T-cell responses? Nature Rev. Immunol. 2008, 8, 231-238.
63. Miles, J.J.; Douek, D.C.; Price, D.A. Bias in the alphabeta T-cell repertoire: Implications for disease pathogenesis and vaccination. Immunol. Cell Biol. 2011, 89, 375-387.
64. Zvyagin, I.V.; Pogorelyy, M.V.; Ivanova, M.E.; Komech, E.A.; Shugay, M.; Bolotin, D.A.; Shelenkov, A.A.; Kurnosov, A.A.; Staroverov, D.B.; Chudakov, D.M.; et al. Distinctive properties of identical twins’ TCR repertoires revealed by high-throughput sequencing. Proc. Natl. Acad. Sci. USA 2014, 111, 5980-5985, doi:10.1073/pnas.1319389111.
65. Williams, W.B.; Liao, H.X.; Moody, M.A.; Kepler, T.B.; Alam, S.M.; Gao, F.; Wiehe, K.; Trama,A.M.; Jones, K,.; Zhang, R.; et al. HIV-1 vaccines. Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies. Science 2015, 349, aab1253, doi:10.1126/science.aab1253.
66. Rolland, M.; Nickle, D.C.; Deng, W.; Frahm, N.; Brander, C.; Learn, G.H.; Heckerman, D.; Jojic, N.; Jojic, V.; Walker, B.D.; et al. Recognition of HIV-1 peptides by host CTL is related to HIV-1 similarity to human proteins. PLoS ONE 2007, 2, e823, doi:10.1371/journal.pone.0000823.
67. Van der Kuyl, A.C. HIV infection and HERV expression: A review. Retrovirology 2012, 9, 6, doi:10.1186/1742-4690-9-6.
68. Seifarth, W.; Frank, O.; Zeilfelder, U.; Spiess, B.; Greenwood, A.D.; Hehlmann, R.; Leib-Mösch, C. Comprehensive analysis of human endogenous retrovirus transcriptional activity in human tissues with a retrovirus-specific microarray. J. Virol. 2005, 79, 341-352, doi:10.1128/JVI.79.1.341-352.2005.
69. Nelson, P.N.; Carnegie, P.R.; Martin, J.; Davari Ejtehadi. H.; Hooley, P.; Roden, D.; Rowland-Jones, S.; Warren, P.; Astley, J.; Murray, P.G. Demystified. Human endogenous retroviruses. Mol. Pathol. 2003, 6, 11-18.
70. Trama, A.M.; Moody, M.A.; Alam, S.M.; Jaeger F.H.; Lockwood, B.; Parks R.; Lloyd, K.E.; Stolarchuk, C.; Scearce, R.; Foulger, A.; et al. HIV-1 envelope gp41 antibodies can originate from terminal ileum B cells that share cross-reactivity with commensal bacteria. Cell Host Microbe 2014, 16, 215-226, doi:10.1016/j.chom.2014.07.003.
71. Borgdorff, H.; Tsivtsivadze, E.; Verhelst, R.; Marzorati, M.; Jurriaans, S.; Ndayisaba, G.F.; Schuren, F.H.; van de Wijgert, J.H. Lactobacillus-dominated cervicovaginal microbiota associated with reduced HIV/STI prevalence and genital HIV viral load in African women. ISME J. 2014, 8, 1781-1793, doi:10.1038/ismej.2014.26.
72. Hearps, A.C.; Tyssen, D.; Srbinovski, D.; Bayigga, L.; Diaz, D.J.; Aldunate, M.; Cone, R.A.; Gugasyan, R.; Anderson, D.J.; Tachedjian, G. Vaginal lactic acid elicits an anti-inflammatory response from human cervicovaginal epithelial cells and inhibits production of pro-inflammatory mediators associated with HIV acquisition. Mucosal Immunol. 2017, in press, doi:10.1038/mi.2017.27.
73. Eade, C.R.; Diaz, C.; Chen, S.; Cole, A.L.; Cole, A.M. HIV-Enhancing factors are secreted by reproductive epithelia upon inoculation with bacterial vaginosis-associated bacteria.protein Pept. Lett. 2015, 22, 672-680.
74. Van de Wijgert, J.H.; Jespers, V. The global health impact of vaginal dysbiosis. Res. Microbiol. 2017, in press, doi:10.1016/j.resmic.2017.02.003.
75. Zabihollahi, R.; Motevaseli, E.; Sadat, S.M.; Azizi-Saraji, A.R.; Asaadi-Dalaie, S.; Modarressi, M.H. Inhibition of HIV and HSV infection by vaginal lactobacilli in vitro and in vivo. DARU J. Pharm. Sci. 2012, 20, 53, doi:10.1186/2008-2231-20z-53.
76. Mirmonsef, P.; Spear, G.T. The barrier to HIV transmission provided by genital tract Lactobacillus colonization. Am. J. Reprod. Immunol. 2014, 1, 531-536, doi:10.1111/aji.12232.
77. Petrova, M.I.; van den Broek, M.; Balzarini, J.; Vanderleyden, J.; Lebeer, S. Vaginal microbiota and its role in HIV transmission and infection. FEMS Microbiol. Rev. 2013, 37, 762-792, doi:10.1111/1574-6976.12029.
78. Ziegler, J.L.; Stites, D.P. Hypothesis: AIDS is an autoimmune disease directed at the immune system and triggered by a lymphotropic retrovirus. Clin. Immunol. Immunopathol. 1986, 41, 305-313.
79. Stott, E.J. Anti-cell antibody in macaques. Nature 1991, 353, 393-395.
80. Kion, T.A.; Hoffmann, G.W. Anti-HIV and anti-anti-MHC antibodies in alloimmune and autoimmune mice. Science 1991, 253, 1138-1140.
81. Hoffmann, G.W.; Kion, T.A.; Grant, M.D. An idiotypic network model of AIDS immunopathogenesis. Proc. Natl. Acad. Sci. USA 1991, 88, 3060-3064.
82. Schacker, T.W.; Reilly, C.; Haase, A.T. Collagen deposition in HIV-1 infected lymphatic tissues and T cell homeostasis. J. Clin. Invest. 2002, 110, 1133-1139, doi:10.1172/JCI16413.
83. Lopalco, L.; Burastero, S.E. HIV-1 and the self-nonself connection: How to sleep with the enemy and be much better off. AIDS Rev. 2008, 10, 162-171.
84. Stratov, I.; DeRose, R.; Purcell, D.F.; Kent, S.J. Vaccines and vaccine strategies against HIV. Curr. Drug Targets 2004, 5, 71-88.
85. Ersching, J.; Pinto, A.R. HIV-1 vaccine clinical trials: the Brazilian experience. Rev. Med. Virol. 2009, 19, 301-311, doi:10.1002/rmv.625.
86. Root-Bernstein, R.S. Five myths about AIDS that are misdirecting research and treatment. Genetica. 1995, 95, 100-132.
87. Keay, S.; Tacket C.O.; Murphy, J.R.; Handwerger, B.S. Anti-CD4 anti-idiotype antibodies in volunteers immunized with rgpl60 or HIV-1 or infected with HIV-1. AIDS Res. Human Retroviruses 1992, 8, 1091-1098.
88. De Santis, C.; Robbioni, P.; Longh,i R.; Lopalco, L.; Siccardi, A.G.; Beretta, A.; Roberts, N.J. Cross-reactive response to human immunodeficiency virus type 1 (HIV-1) gp120 and HLA class I heavy chains induced by receipt of HIV-1-derived envelope vaccines. J. Infect. Dis. 1993, 168, 1396-1403.
89. Zhang, R.; Verkoczy, L.; Wiehe, K.; Alam, S.M.; Nicely, N.I.; Santra, S.; Bradley, T.; Pemble, C.W.; Zhang, J.; Gao, F.; Monefiori, D.C.; et al. Initiation of immune tolerance-controlled HIV gp41 neutralizing B cell lineages. Sci. Trans. Med. 2016, 8, 336ra62, doi:10.1126/scitranslmed.aaf0618.
90. Moody, M.A.; Pedroza-Pacheco, I.; Vandergrift, N.A.; Chui, C.; Lloyd, K.E.; Parks, R.; Soderberg, K.A.; Ogbe, A.T.; Cohen, M.S.; Liao, H.-X.; Gao, F.; et al. Immune perturbations in HIV-1-infected individuals who make broadly neutralizing antibodies. Sci. Immun. 2016, 1, aag0851, doi:10.1126/sciimmunol.aag0851.
91. Bradac, J.; Dieffenbach, C.W. HIV vaccine development: Lessons from the past, informing the future. Invest. Drugs J. 2009, 12, 435-439.
92. Shearer, G.M.; Pinto, L.A.; Clerici, M. Alloimmunization for immune-based therapy and vaccine design against HIV/AIDS. Immunol Today 1999, 20, 66-71.
93. Bourinbaiar, A.; Root-Bernstein, R.S.; Abulafia-Lapid, R.; Rytik, P.G.; Kanev, A.N.; Orlovsky, V.G. Therapeutic HIV vaccines. Curr. Pharm. Design 2006, 12, 2017-2030.
94. Root-Bernstein, R.S.; Bernstein, M. SIV as a human vaccine against HIV? J. Theor. Biol. 1996, 180, 91-92.
95. Kou, Z.C.; Puhr, J.S, Wu, S.S.; Goodenow, M.M.; Sleasman, J.W. Combination antiretroviral therapy results in a rapid increase in T cell receptor variable region β repertoire diversity within CD45RA CD8 T cells in human immunodeficiency virus-infected children. J. Infect. Dis. 2003, 187, 385-395.
96. McFarland, E.J.; Harding, P.A.; Striebich, C.C.; McWhinney, S.; Kuritzkes, D.R.; Kotzin, B.L. Clonal CD8+ T Cell expansions in peripheral blood from human immunodeficiency virus type 1-infected children. J. Infect. Dis. 2002, 186, 477-485.
97. Weekes, M.P.; Carmichael, A.J.; Wills, M.R.; Mynard, K.; Sissons, J.G.P. Human CD38-CD8+ T cells contain greatly expanded functional virus-specific memory CTL clones. J. Immunol. 1999, 162, 7569-7577.
98. Rudensky, A.Y.; Preston-Hurlburt, P.; Hong, S.C.; Barlow, A. Sequence analysis of peptides bound to MHC class II molecules. Nature 1991, 353, 622-627.
99. Cunningham, M.W.; McCormack, J.M.; Fenderson, P.G.; Ho, M.K. Human and murine antibodies crossreactive with streptococcal M protein and myosin recognize the sequence GLN-LYS-SER-LYS-GLN in M protein. J. Immunol. 1989, 143, 2677-2683.
100. Root-Bernstein, R.S.; Podufaly, A. Autoreactive T-cell receptor (Vβ/D/Jβ) sequences in diabetes recognize insulin, the insulin receptor, and each other, and are targets of insulin antibodies. Open Autoimmun. J. 2012, 4, 10-22, doi:10.2174/1876894601204010010.
101. Root-Bernstein, R.S. Rethinking molecular mimicry in rheumatic heart disease and autoimmune myocarditis: Laminin, collagen IV, CAR, and B1AR as initial targets of disease. Front. Ped. Rheumatol. 2014, 2, 85, doi:10.3389/fped.2014.00085.
102. Matsushita, S.; Robert-Guroff, M.; Rusche, J.; Koito, A.; Hattori, T.; Hoshino, H.; Javaherian, K.; Takatsuki, K.; Putney, S. Characterization of a Human immunodeficiency virus neutralizing monoclonal antibody and mapping of the neutralizing epitope. J. Virol. 1998, 62, 2107-2114.
103. Hauber, J.; Perkins, A.; Heimer, E.; Cullen, B. Trans-activation of human immunodeficiency virus gene expression is mediated by nuclear events. Proc. Natl. Acad. Sci. USA 1987, 84, 6364-6368.
104. Rasmussen, L.; Mullenax, J.; Nelson, R.; Merigan, T. Viral polypeptides detected by a complementdependent neutralizing murine monoclonal antibody to human cytomegalovirus. J. Virol. 1985, 55, 274-280.
105. Shugars, D.C.; Smith, M.S.; Glueck, D.H.; Nantermet, P.V.; Seillier-Moiseiwitsch, F.; Swanstrom, R. Analysis of human immunodeficiency virus type 1 nef gene sequences present in vivo. J. Virol. 1993, 67, 4639-4650.
106. Hagen, M.D.; Meyer, K.B.; Kopelman, R.I.; Pauker, S.G. Human immunodeficiency virus infection in health care workers. A method for estimating individual occupational risk. Arch. Intern. Med. 1989, 49, 1541-1544.
107. Boily, M.C.; Baggaley, R.F.; Wang, L.; Masse, B.; White, R.G.; Hayes, R.J.; Heterosexual risk of HIV-1 infection per sexual act: Systematic review and meta-analysis of observational studies. Lancet Infect. Dis. 2009, 9,118-129.
108. Sonnabend, J.A.; Saadoun, S. The acquired immunodeficiency syndrome: A discussion of etiologic hypotheses. AIDS Res. 1983, 1, 107-120.
109. Sonnabend, J.A.; Witkin, S.S.; Purtilo, D.T. A multifactorial model for the development of AIDS in homosexual men. Ann. N. Y. Acad. Sci. 1984, 437, 177-183.
110. Root-Bernstein, R.S. Do we know the cause(s) of AIDS? Persp. Biol. Med. 1990, 33, 480-500.
111. Pattacini, L.; Baeten, J.M.; Thomas, K.K.; Fluharty, T.R.; Murnane, P.M.; Donnell, D.; Bukusi, E.; Ronald, A.; Mugo, N.; Lingappa, J.R.; et al. Regulatory T-cell activity but not conventional HIV-specific T-Cell responses are associated with protection from HIV-1 infection. J. Acquir. Immune Defic. Syndr. 2016, 72, 119-128, doi:10.1097/QAI.0000000000000919.