The CD4C/HIV Nef Transgenic Model of AIDS

Current HIV Research

Volumn 9, Issue 7, 2011, Pages 524-530

  Jolicoeur, Paul ^a,b,c  

^a CLIN RESEARCH INSTITUTE OF MONTREAL   (Canada)

^b UNIVERSITÉ DE MONTRÉAL   (Canada)

^c MCGILL UNIVERSITY   (Canada)

Author keywords

HIV 1; Mouse model; Nef

Indexed keywords

NEF PROTEIN;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ALLELE; ARTICLE; B LYMPHOCYTE ACTIVATION; BYSTANDER EFFECT; CD4+ T LYMPHOCYTE; CD4C HIV NEF MOUSE; CD8+ T LYMPHOCYTE; CELL POPULATION; DENDRITIC CELL; GENE STRUCTURE; GERMINAL CENTER; HELPER CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; IMMUNE DEFICIENCY; LYMPHADENOPATHY; LYMPHOCYTE COUNT; LYMPHOCYTE DEPLETION; LYMPHOCYTE FUNCTION; MOLECULAR MECHANICS; MOUSE STRAIN; NONHUMAN; PATHOGENICITY; PHENOTYPE; PROTEIN EXPRESSION; T LYMPHOCYTE ACTIVATION; T LYMPHOCYTE SUBPOPULATION; THYMUS ATROPHY; TRANSGENE; TRANSGENIC MOUSE;

ACQUIRED IMMUNODEFICIENCY SYNDROME; ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; DISEASE MODELS, ANIMAL; HIV-1; MICE; MICE, TRANSGENIC; NEF GENE PRODUCTS, HUMAN IMMUNODEFICIENCY VIRUS; PHENOTYPE;

EID: 84856475012     PISSN: 1570162X     EISSN: 18734251     Source Type: Journal    
DOI: 10.2174/157016211798842062     Document Type: Article

References (77)

1. Albright AV, Vos RM, Gonzalez-Scarano F. Low-level HIV replication in mixed glial cultures is associated with alterations in the processing of p55(Gag). Virology 2004; 325: 328-39.
2. Ali SA, Huang MB, Campbell PE, et al. Genetic characterization of HIV type 1 Nef-induced vesicle secretion. AIDS Res Hum Retroviruses 2010; 26: 173-92.
3. Anderson CE, Tomlinson GS, Pauly B, et al. Relationship of Nefpositive and GFAP-reactive astrocytes to drug use in early and late HIV infection. Neuropathol Appl Neurobiol 2003; 29: 378-88.
4. Bieniasz PD, Cullen BR. Multiple blocks to human immunodeficiency virus type 1 replication in rodent cells. J Virol 2000; 74: 9868-77.
5. Brack-Werner R, Kleinschmidt A, Ludvigsen A, et al. Infection of human brain cells by HIV-1: restricted virus production in chronically infected human glial cell lines. AIDS 1992; 6: 273-85.
6. Brady HJ, Pennington DJ, Dzierzak EA. Transgenic mice as models of human immunodeficiency virus expression and related cellular effects. J Gen Virol 1994; 75: 2549-58.
7. Brady HJ, Pennington DJ, Miles CG, Dzierzak EA. CD4 cell surface downregulation in HIV-1 Nef transgenic mice is a consequence of intracellular sequestration. EMBO J 1993; 12: 4923-32.
8. Brenchley JM, Paiardini M. Immunodeficiency lentiviral infections in natural and non-natural hosts. Blood 2011; 118: 847-54.
9. Brouillette J, Grandy SA, Jolicoeur P, Fiset C. Cardiac repolarization is prolonged in CD4C/HIV transgenic mice. J Mol Cell Cardiol 2007; 43: 159-67.
10. Brouillette J, Yue P, Fiset C, Jolicoeur P. Delayed cardiac polarization in HIV transgenic mice. Circulation 2001; 104: II-133.
11. Calza L, Manfredi R, Verucchi G. Myocardial infarction risk in HIV-infected patients: epidemiology, pathogenesis, and clinical management. AIDS 2010; 24: 789-802.
12. Chrobak P, Simard MC, Bouchard N, et al. HIV-1 Nef Disrupts Maturation of CD4+ T Cells Through CD4/lck Modulation. J Immunol 2010; 185: 3948-959.
13. Dalgleish AG. Autoimmune mechanisms of depletion of CD4 cells in HIV infection. British J Heamatol 1995; 91: 525-34.
14. de Repentigny L, Aumont F, Ripeau J-S, et al. Mucosal Candidiasis in Transgenic Mice Expressing Human Immunodeficiency Virus Type 1. J Inf Dis 2002; 185: 1103-14.
15. Deacon NJ, Tsykin A, Solomon A, et al. Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients [see comments]. Science 1995; 270: 988-91.
16. Dickie P. HIV type 1 Nef perturbs eye lens development in transgenic mice. AIDS Res Hum Retroviruses 1996; 12: 177-89.
17. Dickie P. Nef modulation of HIV type 1 gene expression and cytopathicity in tissues of HIV transgenic mice. Aids Res & Hum Retroviruses 2000; 16: 777-90.
18. Dickie P, Ramsdell F, Notkins AL, Venkatesan S. Spontaneous and inducible epidermal hyperplasia in transgenic mice expressing HIV-1 Nef. Virology 1993; 197: 431-8.
19. Edelman AS, Zolla-Pazner S. AIDS: a syndrome of immune dysregulation, dysfunction, and deficiency. FASEB J 1989; 3: 22-30.
20. Gorry PR, Howard JL, Churchill MJ, et al. Diminished production of human immunodeficiency virus type 1 in astrocytes results from inefficient translation of gag, env, and nef mRNAs despite efficient expression of Tat and Rev. J Virol 1999; 73: 352-61.
21. Goupil M, Trudelle EB, Dugas V, et al. Macrophage-mediated responses to Candida albicans in mice expressing the human immunodeficiency virus type 1 transgene. Infect Immun 2009; 77: 4136-49.
22. Hanna Z, Kay DG, Cool M, Jothy S, Rebai N, Jolicoeur P. Transgenic mice expressing human immunodeficiency virus type 1 in immune cells develop a severe AIDS-like disease. J Virol 1998; 72: 121-32.
23. Hanna Z, Kay DG, Rebai N, Guimond A, Jothy S, Jolicoeur P. Nef harbors a major determinant of pathogenicity for an AIDS-like disease induced by HIV-1 in transgenic mice. Cell 1998; 95: 163-75.
24. Hanna Z, Priceputu E, Chrobak P, et al. Selective expression of human immunodeficiency virus Nef in specific immune cell populations of transgenic mice is associated with distinct AIDSlike phenotypes. J Virol 2009; 83: 9743-58.
25. Hanna Z, Priceputu E, Hu C, Vincent P, Jolicoeur P. HIV-1 Nef mutations abrogating downregulation of CD4 affect other Nef functions and show reduced pathogenicity in transgenic mice. Virology 2006; 346: 40-52.
26. Hanna Z, Priceputu E, Kay DG, Poudrier J, Chrobak P, Jolicoeur P. In vivo mutational analysis of the N-terminal region of HIV-1 Nef reveals critical motifs for the development of an AIDS-like disease in CD4C/HIV transgenic mice. Virology 2004; 327: 273-86.
27. Hanna Z, Rebai N, Poudrier J, Jolicoeur P. Distinct regulatory elements are required for faithful expression of human CD4 in Tcells, macrophages and dendritic cells of transgenic mice. Blood 2001; 98: 2275-8.
28. Hanna Z, Simard C, Jolicoeur P. Specific expression of the human CD4 gene in mature CD4+CD8-and immature CD4+CD8+T cells, and in macrophages of transgenic mice. Mol Cell Biol 1994; 14: 1084-94.
29. Jacob AJ, Boon NA. HIV cardiomyopathy: a dark cloud with a silver lining? British Heart J 1991; 66: 1-2.
30. James CO, Huang MB, Khan M, Garcia-Barrio M, Powell MD, Bond VC. Extracellular Nef protein targets CD4+ T cells for apoptosis by interacting with CXCR4 surface receptors. J Virol 2004; 78: 3099-109.
31. Jolicoeur P, Yue P, Hanna Z, Simard M-C, Kay DG. Cardiac Disease in HIIV-1 Tg mice. In: Watson RR Ed, AIDS and Heart Disease. New York, Marcel Dekker Inc. 2004; 377-86.
32. Kajiyama W, Kopp JB, Marinos NJ, Klotman PE, Dickie P. Glomerulosclerosis and viral gene expression in HIV-transgenic mice: role of nef. Kidney Int 2000; 58: 1148-59.
33. Kay DG, Yue P, Hanna Z, Jothy S, Tremblay E, Jolicoeur P. Cardiac Disease in Transgenic Mice Expressing Human Immunodeficiency Virus-1 Nef in Cells of the Immune System. Am J Pathol 2002; 161: 321-35.
34. Kestler HW, Ringler DJ, Mori K, et al. Importance of the nef gene for maintenance of high virus loads and for development of AIDS. Cell 1991; 65: 651-62.
35. Kuwata T, Nishimura Y, Whitted S, et al. Association of progressive CD4(+) T cell decline in SIV infection with the induction of autoreactive antibodies. PLoS Pathog 2009; 5: e1000372.
36. Larsen NB, Kestler HW, Docherty JJ. Mice transgenic for simian immunodeficiency virus nef are immunologically compromised. J Biomed Science 1998; 5: 260-6.
37. Lewandowski D, Marquis M, Aumont F, et al. Altered CD4+ Tcell phenotype and function determine the susceptibility to mucosal candidiasis in transgenic mice expressing human immunodeficiency virus type 1. J Immunol 2006; 177: 479-91.
38. Lewis W. Cardiomyopathy in AIDS: a pathophysiological perspective. Prog Cardiovas Dis 2000; 43: 151-70.
39. Li X, Calvo E, Cool M, Chrobak P, Kay DG, Jolicoeur P. Overexpression of Notch1 ectodomain in myeloid cells induces vascular malformations through a paracrine pathway. Am J Pathol 2007; 170: 399-415.
40. Lindemann D, Wilhelm R, Renard P, Althage A, Zinkernagel R, Mous J. Severe immunodeficiency associated with a human immunodeficiency virus 1 NEF/3'-long terminal repeat transgene. J Exp Med 1994; 179: 797-807.
41. Lu TC, He JC, Klotman P. Animal models of HIV-associated nephropathy. Curr Opin Nephrol Hypertens 2006; 15: 233-7.
42. Ludwig E, Silberstein FC, van Empel J, Erfle V, Neumann M, Brack-Werner R. Diminished rev-mediated stimulation of human immunodeficiency virus type 1 protein synthesis is a hallmark of human astrocytes. J Virol 1999; 73: 8279-89.
43. Manz MG. Human-Hemato-Lymphoid-System Mice: Opportunities and Challenges. Immunity 2007; 26: 537-41.
44. Marquis M, Lewandowski D, Dugas V, et al. CD8+ T-cells but not polymorphonuclear leukocytes are required to limit chronic oral carriage of Candida albicans in transgenic mice expressing human immunodeficiency virus type 1. Infect Immunol 2006; 74: 2382-391.
45. Marras D, Bruggeman LA, Gao F, et al. Replication and compartmentalization of HIV-1 in kidney epithelium of patients with HIV-associated nephropathy. Nat Med 2002; 8: 522-6.
46. McCune J, Kaneshima H, Krowka J, et al. The SCID-hu mouse: a small animal model for HIV infection and pathogenesis. Ann Rev Immunol 1991; 9: 399-429.
47. Morse HC, III, McCarty T, Qi CF, et al. B lymphoid neoplasms of mice: characteristics of naturally occurring and engineered diseases and relationships to human disorders. Adv Immunol 2003; 81: 97-121.
48. Mosier DE. Human xenograft models for virus infection. Virology 2000; 271: 215-9.
49. Muratori C, Cavallin LE, Kratzel K, et al. Massive secretion by T cells is caused by HIV Nef in infected cells and by Nef transfer to bystander cells. Cell Host Microbe 2009; 6: 218-30.
50. Neumann M, Felber BK, Kleinschmidt A, Froese B, Erfle V, Pavlakis GNBWR. Restriction of human immunodeficiency virus type 1 production in a human astrocytoma cell line is associated with a cellular block in Rev function. J Virol 1995; 69: 2159-2167.
51. Okada H, Takei R, Tashiro M. Nef protein of HIV-1 induces apoptotic cytolysis of murine lymphoid cells independently of CD95 (Fas) and its suppression by serine/threonine protein kinase inhibitors. FEBS Letters 1997; 417: 61-4.
52. Pennington DJ, Jenkins SA, Brady HJ, Miles CG, Dzierzak EA, Abraham DJ. HIV-I Nef severely impairs thymocyte development and peripheral T-cell function by a CD4-independent mechanism. Genes Funct 1997; 1: 321-35.
53. hi dendritic cells. J Virol 2003; 77: 11733-44.
54. Poudrier J, Weng X, Kay DG, et al. The AIDS Disease of CD4C/HIV Transgenic Mice shows impaired Germinal Centers and Autoantibodies and Develops in the Absence of IFN-g and IL-6. Immunity 2001; 15: 173-85.
55. Priceputu E, Bouallaga I, Zhang Y, et al. Structurally distinct ligang-binding or ligand-independent Notch1 mutants are leukemogenic but affect thymocyte development, apoptosis, and metastasis differently. J Immunol 2006; 177: 2153-66.
56. Priceputu E, Hanna Z, Hu C, et al. Primary human immunodeficiency virus type 1 nef alleles show major differences in pathogenicity in transgenic mice. J Virol 2007; 81: 4677-4693.
57. Priceputu E, Rodrigue I, Chrobak P, et al. The Nef-mediated AIDS-like disease of CD4C/HIV transgenic mice is associated with increased Fas/FasL expression on T cells and T cell death, but is not prevented in Fas, FasL, TNFR-1 and ICE deficient nor in Bcl2-expressing transgenic mice. J Virol 2005; 79: 6377-91.
58. Qiao X, He B, Chiu A, Knowles DM, Chadburn A, Cerutti A. Human immunodeficiency virus 1 Nef suppresses CD40-dependent immunoglobulin class switching in bystander B cells. Nat Immunol 2006; 7: 302-10.
59. Rahim MM, Chrobak P, Hu C, Hanna Z, Jolicoeur P. Adult AIDSlike disease in a novel inducible human immunodeficiency virus type 1 Nef transgenic mouse model: CD4+ T-cell activation is Nef dependent and can occur in the absence of lymphophenia. J Virol 2009; 83: 11830-46.
60. Ranki A, Nyberg M, Ovod V, et al. Abundant expression of hiv nef and rev proteins in brain astrocytes in vivo is associated with dementia. AIDS 1995; 9: 1001-8.
61. Raymond AD, Campbell-Sims TC, Khan M, et al. HIV Type 1 Nef is released from infected cells in CD45(+) microvesicles and is present in the plasma of HIV-infected individuals. AIDS Res Hum Retroviruses 2011; 27: 167-78.
62. Rosenberg ZF, Fauci AS. The immunopathogenesis of HIV infection. Adv Immunol 1989; 47: 377-431.
63. Rowland-Jones S, Dong T. Dying T cells trigger autoimmunity in HIV. Nat Med 2007; 13: 1413-5.
64. Saito Y, Sharer LR, Epstein LG, et al. Overexpression of nef as a marker for restricted HIV-1 infection of astrocytes in postmortem pediatric central nervous tissues. Neurology 1994; 44: 474-81.
65. Shannon RP. SIV cardiomyopathy in non-human primates. Trends Cardiovasc Med 2001; 11: 242-6.
66. Shultz LD, Ishikawa F, Greiner DL. Humanized mice in translational biomedical research. Nat Rev Immunol 2007; 7: 118-30.
67. Simard M-C, Chrobak P, Kay DG, Hanna Z, Jothy S, Jolicoeur P. Expression of Simian Immunodeficiency Virus nef in immune cells of transgenic mice leads to a severe AIDS-like disease. J Virol 2002; 76: 3981-95.
68. Sipsas NV, Kokori SI, Ioannidis JP, Kyriaki D, Tzioufas AG, Kordossis T. Circulating autoantibodies to erythropoietin are associated with human immunodeficiency virus type 1-related anemia. J Infect Dis 1999; 180: 2044-7.
69. Skowronski J, Parks D, Mariani R. Altered T cell activation and development in transgenic mice expressing the HIV-1 nef gene. Embo J 1993; 12: 703-13.
70. Stohl W, Cheema GS, Briggs WS, et al. B lymphocyte stimulator protein-associated increase in circulating autoantibody levels may require CD4+ T cells: lessons from HIV-infected patients. Clin Immunol 2002; 104: 115-22.
71. Stratton R, Slapak G, Mahungu T, Kinloch-De Loes S. Autoimmunity and HIV. Curr Opin Infect Dis 2009; 22: 49-56.
72. Swingler S, Zhou J, Swingler C, et al. Evidence for a pathogenic determinant in HIV-1 Nef involved in B cell dysfunction in HIV/AIDS. Cell Host Microbe 2008; 4: 63-76.
73. Tinkle BT, Ueda H, Jay G. The pathogenic role of human immunodeficiency virus accessory genes in transgenic mice. Curr Topics Micro & Immuno 1995; 193: 133-56.
74. Van Duyne R, Pedati C, Guendel I, et al. The utilization of humanized mouse models for the study of human retroviral infections. Retrovirology 2009; 6: 76.
75. Vincent P, Priceputu E, Kay D, Saksela K, Jolicoeur P, Hanna Z. Activation of p21-activated kinase 2 and its association with Nef are conserved in murine cells but are not sufficient to induce an AIDS-like disease in CD4C/HIV transgenic mice. J Biol Chem 2006; 281: 6940-54.
76. Wang Z, Horowitz HW, Orlikowsky T, et al. Polyspecific selfreactive antibodies in individuals infected with human immunodeficiency virus facilitate T cell deletion and inhibit costimulatory accessory cell function. J Inf Dis 1999; 180: 1072-9.
77. Weng X, Priceputu E, Chrobak P, et al. CD4 T cells from CD4C/HIV nef transgenic mice show enhanced activation in vivo with impaired proliferation in vitro, but are dispensable for the development of a severe AIDS-like organ disease. J Virol 2004; 78: 5244-57.