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Novel Mouse Models for Understanding HIV-1 Pathogenesis

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HIV Protocols

Part of the book series: Methods In Molecular Biology™ ((MIMB,volume 485))

Abstract

Small animal models in which in vivo HIV-1 infection, pathogenesis, and immune responses can be studied would permit both basic research on the biology of the disease, as well as a system to rapidly screen developmental therapeutics and/or vaccines. To date, the most widely-used models have been the severe combined immunodeficient (SCID)-hu (also known as the thy/liv SCID-hu) and the huPBL-SCID mouse models. Recently three new models have emerged, i.e., the intrasplenic huPBL/SPL-SCID model, the NOD/SCID/IL2Rγnull mouse model, and the $Rag2-/-γc -/- mouse model. Details on the construction, maintenance and HIV-1 infection of these models are discussed.

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References

  1. An, D. S., Poon, B., Fang, R. H., et al. (2007) Use of a novel chimeric mouse model with a functionally active human immune system to study human immunodeficiency virus type 1 infection. Clin Vaccine Immunol 14, 391–396.

    Article  CAS  PubMed  Google Scholar 

  2. Baenziger, S., Tussiwand, R., Schlaepfer, E., et al. (2006) Disseminated and sustained HIV infection in CD34+ cord blood cell-transplanted Rag2-/-gamma c-/- mice. Proc Natl Acad Sci U S A 103, 15951– 15956.

    Article  CAS  PubMed  Google Scholar 

  3. Berges, B. K., Wheat, W. H., Palmer, B. E., et al. (2006) HIV-1 infection and CD4 T cell depletion in the humanized Rag2-/-gamma c-/- (RAG-hu) mouse model. Retrovirology 3, 76.

    Article  PubMed  Google Scholar 

  4. Borkow, G. (2005) Mouse models for HIV-1 infection. IUBMB Life 57, 819–823.

    Article  CAS  PubMed  Google Scholar 

  5. Bosma, M. J., Carroll, A. M. (1991) The SCID mouse mutant: definition, characterization, and potential uses. Annu Rev Immunol 9, 323–350.

    Article  CAS  PubMed  Google Scholar 

  6. Cao, X., Shores, E. W., Hu-Li, J., et al. (1995) Defective lymphoid development in mice lacking expression of the common cytokine receptor gamma chain. Immunity 2, 223–238.

    Article  CAS  PubMed  Google Scholar 

  7. Chicha, L., Tussiwand, R., Traggiai, E., et al. (2005) Human adaptive immune system Rag2-/-gamma(c)-/- mice. Ann N Y Acad Sci 1044, 236–243.

    Article  CAS  PubMed  Google Scholar 

  8. De Maria, A., Cirillo, C., Moretta, L. (1994) Occurrence of human immunodeficiency virus type 1 (HIV-1)-specific cytolytic T cell activity in apparently uninfected children born to HIV-1-infected mothers. J Infect Dis 170, 1296–1299.

    PubMed  Google Scholar 

  9. DiSanto, J. P., Muller, W., Guy-Grand, D., et al. (1995) Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor gamma chain. Proc Natl Acad Sci U S A 92, 377–381.

    Article  CAS  PubMed  Google Scholar 

  10. Ferbas, J., Kaplan, A. H., Hausner, M. A., et al. (1995) Virus burden in long-term survivors of human immunodeficiency virus (HIV) infection is a determinant of anti-HIV CD8+ lymphocyte activity. J Infect Dis 172, 329–339.

    CAS  PubMed  Google Scholar 

  11. Garcia, S., Dadaglio, G., Gougeon, M. L. (1997) Limits of the human-PBL-SCID mice model: severe restriction of the V beta T-cell repertoire of engrafted human T cells. Blood 89, 329–336.

    CAS  PubMed  Google Scholar 

  12. Gimeno, R., Weijer, K., Voordouw, A., et al. (2004) Monitoring the effect of gene silencing by RNA interference in human CD34+ cells injected into newborn RAG2-/- gammac-/- mice: functional inactivation of p53 in developing T cells. Blood 104, 3886–3893.

    Article  CAS  PubMed  Google Scholar 

  13. Goldman, J. P., Blundell, M. P., Lopes, L., et al. (1998) Enhanced human cell engraftment in mice deficient in RAG2 and the common cytokine receptor gamma chain. Br J Haematol 103, 335–342.

    Article  CAS  PubMed  Google Scholar 

  14. Goldstein, H., Pettoello-Mantovani, M., Katopodis, N. F., et al. (1996) SCID-hu mice: a model for studying disseminated HIV infection. Semin Immunol 8, 223–231.

    Article  CAS  PubMed  Google Scholar 

  15. Gorantla, S., Sneller, H., Walters, L., et al. (2007) Human immunodeficiency virus type 1 pathobiology studied in humanized BALB/c-Rag2-/-gammac-/- mice. J Virol 81, 2700–2712.

    Article  CAS  PubMed  Google Scholar 

  16. Gotch, F., Gallimore, A., McMichael, A. (1996) Cytotoxic T cells–protection from disease progression–protection from infection. Immunol Lett 51, 125–128.

    Article  CAS  PubMed  Google Scholar 

  17. Goulder, P. J., Phillips, R. E., Colbert, R. A., et al. (1997) Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS. Nat Med 3, 212–217.

    Article  CAS  PubMed  Google Scholar 

  18. Harrer, T., Harrer, E., Kalams, S. A., et al. (1996) Cytotoxic T lymphocytes in asymptomatic long-term nonprogressing HIV-1 infection. Breadth and specificity of the response and relation to in vivo viral quasispecies in a person with prolonged infection and low viral load. J Immunol 156, 2616–2623.

    CAS  PubMed  Google Scholar 

  19. Hiramatsu, H., Nishikomori, R., Heike, T., et al. (2003) Complete reconstitution of human lymphocytes from cord blood CD34+ cells using the NOD/SCID/gammacnull mice model. Blood 102, 873–880.

    Article  CAS  PubMed  Google Scholar 

  20. Huynen, M. A., Neumann, A. U. (1996) Rate of killing of HIV-infected T cells and disease progression. Science 272, 1962.

    Article  CAS  PubMed  Google Scholar 

  21. Ishikawa, F., Yasukawa, M., Lyons, B., et al. (2005) Development of functional human blood and immune systems in NOD/SCID/IL2 receptor {gamma} chain(null) mice. Blood 106, 1565– 1573.

    Article  CAS  PubMed  Google Scholar 

  22. Ito, M., Hiramatsu, H., Kobayashi, K., et al. (2002) NOD/SCID/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells. Blood 100, 3175–3182.

    Article  CAS  PubMed  Google Scholar 

  23. Jassoy, C., Walker, B. D. (1997) HIV-1-specific cytotoxic T lymphocytes and the control of HIV-1 replication. Springer Semin Immunopathol 18, 341–354.

    Article  CAS  PubMed  Google Scholar 

  24. Joseph, A., Zheng, J. H., Follenzi, A., et al. (2008) Lentiviral vectors encoding human immunodeficiency virus type 1 (HIV-1)-specific T-cell receptor genes efficiently convert peripheral blood CD8 T lymphocytes into cytotoxic T lymphocytes with potent in vitro and in vivo HIV-1-specific inhibitory activity. J Virol 82, 3078–89.

    Article  CAS  PubMed  Google Scholar 

  25. Joseph, A., Zheng, J., Patel, M., et al. (2007) An intrasplenic huPBL/SPL SCID model for the study of acute in vivo CTL activity against HIV-1 infected cells. In preparation.

    Google Scholar 

  26. Kan-Mitchell, J., Bisikirska, B., Wong-Staal, F., et al. (2004) The HIV-1 HLA-A2-SLYNTVATL is a help-independent CTL epitope. J Immunol 172, 5249–5261.

    CAS  PubMed  Google Scholar 

  27. Kollmann, T. R., Kim, A., Pettoello-Mantovani, M., et al. (1995) Divergent effects of chronic HIV-1 infection on human thymocyte maturation in SCID-hu mice. J Immunol 154, 907–921.

    CAS  PubMed  Google Scholar 

  28. Kollmann, T. R., Pettoello-Mantovani, M., Zhuang, X., et al. (1994) Disseminated human immunodeficiency virus 1 (HIV-1) infection in SCID- hu mice after peripheral inoculation with HIV-1. J Exp Med 179, 513–522.

    Article  CAS  PubMed  Google Scholar 

  29. Koup, R. A., Safrit, J. T., Cao, Y., et al. (1994) Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J Virol 68, 4650–4655.

    CAS  PubMed  Google Scholar 

  30. LaBarre, D. D., Lowy, R. J. (2001) Improvements in methods for calculating virus titer estimates from TCID50 and plaque assays. J Virol Methods 96, 107–126.

    Article  CAS  PubMed  Google Scholar 

  31. Langlade-Demoyen, P., Ngo-Giang-Huong, N., Ferchal, F., et al. (1994) Human immunodeficiency virus (HIV) nef-specific cytotoxic T lymphocytes in noninfected heterosexual contact of HIV-infected patients. J Clin Invest 93, 1293–1297.

    Article  CAS  PubMed  Google Scholar 

  32. Markham, R. B., Donnenberg, A. D. (1992) Effect of donor and recipient immunization protocols on primary and secondary human antibody responses in SCID mice reconstituted with human peripheral blood mononuclear cells. Infect Immun 60, 2305–2308.

    CAS  PubMed  Google Scholar 

  33. Mazurier, F., Fontanellas, A., Salesse, S., et al. (1999) A novel immunodeficient mouse model–RAG2 x common cytokine receptor gamma chain double mutants–requiring exogenous cytokine administration for human hematopoietic stem cell engraftment. J Interferon Cytokine Res 19, 533–541.

    Article  CAS  PubMed  Google Scholar 

  34. McCune, J. M. (1991) SCID mice as immune system models. Curr Opin Immunol 3, 224–228.

    Article  CAS  PubMed  Google Scholar 

  35. McCune, J. M., Namikawa, R., Kaneshima, H., et al. (1988) The SCID-hu mouse: murine model for the analysis of human hematolymphoid differentiation and function. Science 241, 1632–1639.

    Article  CAS  PubMed  Google Scholar 

  36. McMichael, A. J., Rowland-Jones, S. L. (2001) Cellular immune responses to HIV. Nature 410, 980–987.

    Article  CAS  PubMed  Google Scholar 

  37. Mosier, D. E. (1996) Modeling AIDS in a mouse. Hosp Pract (Minneap), 31, 41–48, 53–45, 59–60.

    CAS  Google Scholar 

  38. Mosier, D. E. (1996) Viral pathogenesis in hu-PBL-SCID mice. Semin Immunol 8, 255–262.

    Article  CAS  PubMed  Google Scholar 

  39. Mosier, D. E., Gulizia, R. J., Baird, S. M., et al. (1988) Transfer of a functional human immune system to mice with severe combined immunodeficiency. Nature 335, 256–259.

    Article  CAS  PubMed  Google Scholar 

  40. Mosier, D. E., Gulizia, R. J., Baird, S. M., et al. (1991) Human immunodeficiency virus infection of human-PBL-SCID mice. Science 251, 791–794.

    Article  CAS  PubMed  Google Scholar 

  41. Musey, L., Hughes, J., Schacker, T., et al. (1997) Cytotoxic-T-cell responses, viral load, and disease progression in early human immunodeficiency virus type 1 infection. N Engl J Med 337, 1267–1274.

    Article  CAS  PubMed  Google Scholar 

  42. Namikawa, R., Weilbaecher, K. N., Kaneshima, H., et al. (1990) Long-term human hematopoiesis in the SCID-hu mouse. J Exp Med 172, 1055–1063.

    Article  CAS  PubMed  Google Scholar 

  43. Ogg, G. S., Jin, X., Bonhoeffer, S., et al. (1998) Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA. Science 279, 2103–2106.

    Article  CAS  PubMed  Google Scholar 

  44. Pantaleo, G., Demarest, J. F., Soudeyns, H., et al. (1994) Major expansion of CD8+ T cells with a predominant V beta usage during the primary immune response to HIV. Nature 370, 463–467.

    Article  CAS  PubMed  Google Scholar 

  45. Pettoello-Mantovani, M., Kollmann, T. R., Katopodis, N. F., et al. (1998) thy/liv-SCID-hu mice: a system for investigating the in vivo effects of multidrug therapy on plasma viremia and human immunodeficiency virus replication in lymphoid tissues. J Infect Dis 177, 337–346.

    Article  CAS  PubMed  Google Scholar 

  46. Phillips, R. E., Rowland-Jones, S., Nixon, D. F., et al. (1991) Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition. Nature 354, 453–459.

    Article  CAS  PubMed  Google Scholar 

  47. Rinaldo, C., Huang, X. L., Fan, Z. F., et al. (1995) High levels of anti-human immunodeficiency virus type 1 (HIV-1) memory cytotoxic T-lymphocyte activity and low viral load are associated with lack of disease in HIV-1-infected long-term nonprogressors. J Virol 69, 5838–5842.

    CAS  PubMed  Google Scholar 

  48. Roncarolo, M. G., Carballido, J. M., Rouleau, M., et al. (1996) Human T-and B-cell functions in SCID-hu mice. Semin Immunol 8, 207–213.

    Article  CAS  PubMed  Google Scholar 

  49. Rowland-Jones, S., Sutton, J., Ariyoshi, K., et al. (1995) HIV-specific cytotoxic T-cells in HIV-exposed but uninfected Gambian women. Nat Med 1, 59–64.

    Article  PubMed  Google Scholar 

  50. Rowland-Jones, S. L., Dong, T., Fowke, K. R., et al. (1998) Cytotoxic T cell responses to multiple conserved HIV epitopes in HIV-resistant prostitutes in Nairobi. J Clin Invest 102, 1758–1765.

    Article  CAS  PubMed  Google Scholar 

  51. Sango, K., Joseph, A., Buhl, S., et al. (2007) HIV-1 specific humoral responses induced by intrasplenic infection of HIV-1 in a humanized Rag2-/-gamma-common-chain-/- mouse model. In preparation.

    Google Scholar 

  52. Saxon, A., Macy, E., Denis, K., et al. (1991) Limited B cell repertoire in severe combined immunodeficient mice engrafted with peripheral blood mononuclear cells derived from immunodeficient or normal humans. J Clin Invest 87, 658–665.

    Article  CAS  PubMed  Google Scholar 

  53. Shinkai, Y., Rathbun, G., Lam, K. P., et al. (1992) RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell 68, 855–867.

    Article  CAS  PubMed  Google Scholar 

  54. Shultz, L. D., Lyons, B. L., Burzenski, L. M., et al. (2005) Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J Immunol 174, 6477–6489.

    CAS  PubMed  Google Scholar 

  55. Somasundaram, R., Jacob, L., Adachi, K., et al. (1995) Limitations of the severe combined immunodeficiency (SCID) mouse model for study of human B-cell responses. Scand J Immunol 41, 384–390.

    Article  CAS  PubMed  Google Scholar 

  56. Tary-Lehmann, M., Saxon, A., Lehmann, P. V. (1995) The human immune system in hu-PBL-SCID mice. Immunol Today 16, 529–533.

    Article  CAS  PubMed  Google Scholar 

  57. Traggiai, E., Chicha, L., Mazzucchelli, L., Bronz, L., Piffaretti, J. C., Lanzavecchia, A. and Manz, M. G. (2004) Development of a human adaptive immune system in cord blood cell-transplanted mice. Science 304, 104–107.

    Article  CAS  PubMed  Google Scholar 

  58. Watanabe, S., Terashima, K., Ohta, S., et al. (2007) Hematopoietic stem cell-engrafted NOD/SCID/IL2Rgamma null mice develop human lymphoid systems and induce long-lasting HIV-1 infection with specific humoral immune responses. Blood 109, p212–218.

    Article  CAS  PubMed  Google Scholar 

  59. Weijer, K., Uittenbogaart, C. H., Voordouw, A., et al. (2002) Intrathymic and extrathymic development of human plasmacytoid dendritic cell precursors in vivo. Blood 99, 2752–2759.

    Article  CAS  PubMed  Google Scholar 

  60. Wolinsky, S. M., Korber, B. T., Neumann, A. U., et al. (1996) Adaptive evolution of human immunodeficiency virus-type 1 during the natural course of infection. Science 272, 537–542.

    Article  CAS  PubMed  Google Scholar 

  61. Zhang, L., Kovalev, G. I., Su, L. (2007) HIV-1 infection and pathogenesis in a novel humanized mouse model. Blood 109, 2978–2981.

    CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the National Institutes of Health (National Institute of Allergy and Infectious Diseases AI67136, and the Einstein/MMC Center for AIDS Research AI51519).

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA

    Aviva Joseph, Kaori Sango & Harris Goldstein

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  1. Aviva Joseph
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  2. Kaori Sango
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  3. Harris Goldstein
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Editors and Affiliations

  1. Albert Einstein College of Medicine, Bronx, NY, USA

    Vinayaka R. Prasad PhD  & Ganjam V. Kalpana PhD  & 

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Joseph, A., Sango, K., Goldstein, H. (2009). Novel Mouse Models for Understanding HIV-1 Pathogenesis. In: Prasad, V.R., Kalpana, G.V. (eds) HIV Protocols. Methods In Molecular Biology™, vol 485. Humana Press. https://doi.org/10.1007/978-1-59745-170-3_21

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  • DOI: https://doi.org/10.1007/978-1-59745-170-3_21

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-859-1

  • Online ISBN: 978-1-59745-170-3

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