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Humanized Mice for Human Retrovirus Infection

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Humanized Mice

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 324))

Inbred mice with specific genetic defects have greatly facilitated the analysis of complex biological events. Several humanized mouse models using the C.B.-17 scid/scid mouse (referred to as the SCID mouse) have been created from two transplantation protocols, and these mice have been utilized for the investigation of human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus type I (HTLV-I) pathogenesis and the evaluation of antiviral compounds. To generate a more prominent small animal model for human retrovirus infection, especially for examination of the pathological process and the immune reaction, a novel immunodeficient mouse strain derived from the NOD SCID mouse was created by backcrossing with a common γ chain (γc )-knockout mouse. The NOD-SCID γc null (NOG) mouse has neither functional T and B cells nor NK cells and has been used as a recipient in humanized mouse models for transplantation of human immune cells particularly including hematopoietic stem cells (HSC). From recent advances in development of humanized mice, we are now able to provide a new version of the animal model for human retrovirus infection and human immunity.

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References

  • Aldrovandi GM, Feuer G, Gao L, Jamieson B, Kristeva M, Chen IS, Zack JA (1993) The SCID-hu mouse as a model for HIV-1 infection. Nature 363:732–736.

    Article  PubMed  CAS  Google Scholar 

  • Baenziger S, Tussiwand R, Schlaepfer E, Mazzucchelli L, Heikenwalder M, Kurrer MO, Behnke S, Frey J, Oxenius A, Joller H, Aguzzi A, Manz MG, Speck RF (2006) Disseminated and sustained HIV infection in CD34+ cord blood cell-transplanted Rag2−/−gamma c−/− mice. Proc Natl Acad Sci USA 103:15951–15956.

    Article  PubMed  CAS  Google Scholar 

  • Berges BK, Wheat WH, Palmer BE, Connick E, Akkina R (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 

  • Blunt T, Finnie NJ, Taccioli GE, Smith GC, Demengeot J, Gottlieb TM, Mizuta R, Varghese AJ, Alt FW, Jeggo PA et al. (1995) Defective DNA-dependent protein kinase activity is linked to VDJ recombination and DNA repair defects associated with the murine scid mutation. Cell 80:813–823.

    Article  PubMed  CAS  Google Scholar 

  • Bonyhadi ML, Rabin L, Salimi S, Brown DA, Kosek J, McCune JM, Kaneshima (1993) HIV induces thymus depletion in vivo. Nature 363:728–732.

    Article  PubMed  CAS  Google Scholar 

  • Bosma GC, Custer RP, Bosma MJ (1983) A severe combined immunodeficiency mutation in the mouse. Nature 301:527–530.

    Article  PubMed  CAS  Google Scholar 

  • Boubnov NV, Weaver DT (1995) scid cells are deficient in Ku and replication protein A phosphorylation by the DNA-dependent protein kinase. Mol Cell Biol 15:5700–5706.

    PubMed  CAS  Google Scholar 

  • Delhem N, F Hadida, G Gorochov, F Carpentier, JP de Cavel, JF Andreani, B Autran, JY Cesbron (1998) Primary Th1 cell immunization against HIVgp160 in SCID-hu mice coengrafted with peripheral blood lymphocytes and skin. J Immunol 161:2060–2069.

    PubMed  CAS  Google Scholar 

  • Dewan MZ, Terashima K, Taruishi M, Hasegawa H, Ito M, Tanaka Y, Mori N, Sata T, Koyanagi Y, Maeda M, Kubuki Y, Okayama A, Fujii M, Yamamoto N (2003) Rapid tumor formation of human T-cell leukemia virus type 1-infected cell lines in novel NOD-SCID/γcnull mice: suppression by an inhibitor against NF-kappaB. J Virol 77:5286–5294.

    Article  PubMed  CAS  Google Scholar 

  • Dewan MZ, Uchihara JN, Terashima K, Honda M, Sata T, Ito M, Fujii N, Uozumi K, Tsukasaki K, Tomonaga M, Kubuki Y, Okayama A, Toi M, Mori N, Yamamoto N (2006) Efficient intervention of growth and infiltration of primary adult T-cell leukemia cells by an HIV protease inhibitor, ritonavir. Blood 107:716–724.

    Article  PubMed  CAS  Google Scholar 

  • Gorantla S, Santos K, Meyer V, Dewhurst S, Bowers WJ, Federoff HJ, Gendelman HE, Poluektova L (2005) Human dendritic cells transduced with herpes simplex virus amplicons encoding human immunodeficiency virus type 1 (HIV-1) gp120 elicit adaptive immune responses from human cells engrafted into NOD/SCID mice and confer partial protection against HIV-1 challenge. J Virol 79:2124–2132.

    Article  PubMed  CAS  Google Scholar 

  • Hartley O, Gaertner H, Wilken J, Thompson D, Fish R, Ramos A, Pastore C, Dufour B, Cerini F, Melotti A, Heveker N, Picard L, Alizon M, Mosier D, Kent S, Offord R (2004) Medicinal chemistry applied to a synthetic protein: development of highly potent HIV entry inhibitors. Proc Natl Acad Sci USA 101:16460–16465.

    Article  PubMed  CAS  Google Scholar 

  • Hinuma Y, Nagata K, Hanaoka M, Nakai M, Matsumoto T, Kinoshita KI, Shirakawa S, Miyoshi I (1981) Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera. Proc Natl Acad Sci USA 78:6476–6480.

    Article  PubMed  CAS  Google Scholar 

  • Hiramatsu H, Nishikomori R, Heike T, Ito M, Kobayashi K, Katamura K, Nakahata T (2003) Complete reconstitution of human lymphocytes from cord blood CD34+ cells using the NOD/SCID/γc null mice model. Blood 102:873–880.

    Article  PubMed  CAS  Google Scholar 

  • Ifversen P, Borrebaeck CA (1996) SCID-hu-PBL: a model for making human antibodies? Semin Immunol 8:243–248.

    Article  PubMed  CAS  Google Scholar 

  • Imada K, Takaori-Kondo A, Akagi T, Shimotohno K, Sugamura K, Hattori T, Yamabe H, Okuma M, Uchiyama T (1995) Tumorigenicity of human T-cell leukemia virus type I-infected cell lines in severe combined immunodeficient mice and characterization of the cells proliferating in vivo. Blood 86:2350–2357.

    PubMed  CAS  Google Scholar 

  • Ishikawa F, Yasukawa M, Lyons B, Yoshida S, Miyamoto T, Yoshimoto G, Watanabe T, Akashi K, Shultz LD, Harada M (2005) Development of functional human blood and immune systems in γ chainnull mice. Blood 106:1565–1573.

    Article  PubMed  CAS  Google Scholar 

  • Ito M, Hiramatsu H, Kobayashi K, Suzue K, Kawahata M, Hioki K, Ueyama Y, Koyanagi Y, Sugamura K, Tsuji K, Heike T, Nakahata T (2002) NOD/SCID/γc nullmouse: an excellent recipient mouse model for engraftment of human cells. Blood 100:3175–3182.

    Article  PubMed  CAS  Google Scholar 

  • Jamieson BD, Zack JA (1999) Murine models for HIV disease. AIDS 13 Suppl A:S5–11.

    PubMed  Google Scholar 

  • Kaneshima H, Shih CC, Namikawa R, Rabin L, Outzen H, Machado SG, McCune JM (1991) Human immunodeficiency virus infection of human lymph nodes in the SCID/hu mouse. Proc Natl Acad Sci USA 88:4523–4527.

    Article  PubMed  CAS  Google Scholar 

  • Kaneshima H, Su L, Bonyhadi ML, Connor RI, Ho DD, McCune JM (1994) Rapid-high, syncytium-inducing isolates of human immunodeficiency virus type 1 induce cytopathicity in the human thymus of the SCID-hu mouse. J Virol 68:8188–8192.

    PubMed  CAS  Google Scholar 

  • Kawano Y, Tanaka Y, Misawa N, Tanaka R, Kira JI, Kimura T, Fukushi M, Sano K, Goto T, Nakai M, Kobayashi T, Yamamoto N, Koyanagi Y (1997) Mutational analysis of human immunodeficiency virus type 1 (HIV-1) accessory genes: requirement of a site in the nef gene for HIV-1 replication in activated CD4+ T cells in vitro and in vivo. J Virol 1:8456–8466.

    Google Scholar 

  • Kirchgessner CU, Patil CK, Evans JW, Cuomo CA, Fried LM, Carter T, Oettinger MA, Brown JM (1995) DNA-dependent kinase (p350) as a candidate gene for the murine SCID defect. Science 267:1178–1183.

    Article  PubMed  CAS  Google Scholar 

  • Koyanagi Y, Tanaka Y, Kira J, Ito M, Hioki K, Misawa N, Kawano Y, Yamasaki K, Tanaka R, Suzuki Y, Ueyama Y, Terada E, Tanaka T, Miyasaka M, Kobayashi T, Kumazawa Y, Yamamoto N (1997a) Primary human immunodeficiency virus type 1 viremia and central nervous system invasion in a novel hu-PBL-immunodeficient mouse strain. J Virol 71:2417–2424.

    PubMed  CAS  Google Scholar 

  • Koyanagi Y, Tanaka Y, Tanaka R, Misawa N, Kawano Y, Tanaka T, Miyasaka M, Ito M, Ueyama Y, Yamamoto N (1997b) High levels of viremia in hu-PBL-NOD-scid with HIV-1 infection. Leukemia 11 Suppl 3:109–112.

    Google Scholar 

  • Lu W, LC Arraes, WT Ferreira, J-M Andrieu (2004) Therapeutic dendritic-cell vaccine for chronic HIV-1 infection. Nat Med 10:1359–1365.

    Article  PubMed  CAS  Google Scholar 

  • Lu W, X Wu, Y Lu, W Guo, JM Andrieu (2003) Therapeutic dendritic-cell vaccine for simian AIDS. Nat Med 9:27–32.

    Article  PubMed  CAS  Google Scholar 

  • McCune JM, Kaneshima H, Krowka J, Namikawa R, Outzen H, Peault B, Rabin L, Shih CC, Yee E, Lieberman M et al. (1988) The SCID-hu mouse: murine model for the analysis of human hematolymphoid differentiation and function. Science 241:1632–1639.

    Article  PubMed  CAS  Google Scholar 

  • McCune JM, Kaneshima H, Krowka J, Namikawa R, Outzen H, Peault B, Rabin L, Shih CC, Yee E, Lieberman M et al. (1991) The SCID-hu mouse: a small animal model for HIV infection and pathogenesis. Annu Rev Immunol 9:399–429.

    Article  PubMed  CAS  Google Scholar 

  • McCune JM, Namikawa R, Shih CC, Rabin L, Kaneshima H (1990) Suppression of HIV infection in AZT-treated SCID/hu mice. Science 247:564–566.

    Article  PubMed  CAS  Google Scholar 

  • Miller RD, Hogg J, Ozaki JH, Gell D, Jackson SP, Riblet R (1995) Gene for the catalytic subunit of mouse DNA-dependent protein kinase maps to the scid locus. Proc Natl Acad Sci USA 92:10792–10795.

    Article  PubMed  CAS  Google Scholar 

  • Miura Y, Misawa N, Kawano Y, Okada H, Inagaki Y, Yamamoto N, Ito M, Yagita H, Okumura K, Mizusawa H, Koyanagi Y (2003) Tumor necrosis factor-related apoptosis-inducing ligand induces neuronal death in a murine model of HIV central nervous system infection. Proc Natl Acad Sci USA 100:2777–2782.

    Article  PubMed  CAS  Google Scholar 

  • Miura Y, Misawa N, Maeda N, Inagaki Y, Tanaka Y, Ito M, Kayagaki N, Yamamoto N, Yagita H, Mizusawa H, Koyanagi Y (2001) Critical contribution of TNF-related apoptosis-inducing ligand (TRAIL) to apoptosis of human CD4+ T cells in HIV-1-infected hu-PBL-NOD-SCID mice. J Exp Med 193:651–659.

    Article  PubMed  CAS  Google Scholar 

  • Mori N, Fujii M, Ikeda S, Yamada Y, Tomonaga M, Ballard DW, Yamamoto N (1999) Constitutive activation of NF-kappaB in primary adult T-cell leukemia cells. Blood 93:2360–2368.

    PubMed  CAS  Google Scholar 

  • Mosier DE, Gulizia RJ, Baird SM, Wilson DB (1988) Transfer of a functional human immune system to mice with severe combined immunodeficiency. Nature 335:256–259.

    Article  PubMed  CAS  Google Scholar 

  • Mosier DE, Gulizia RJ, Baird SM, Wilson DB, Spector DH, Spector SA (1991) Human immunodeficiency virus infection of human-PBL-SCID mice. Science 251:791–794.

    Article  PubMed  CAS  Google Scholar 

  • Mosier DE, Gulizia RJ, MacIsaac PD, Torbett BE, Levy JA (1993) Rapid loss of CD4+ T cells in human-PBL-SCID mice by noncytopathic HIV isolates. Science 260:689–692.

    Article  PubMed  CAS  Google Scholar 

  • Nakata H, Maeda K, Miyakawa T, Shibayama S, Matsuo M, Takaoka Y, Ito M, Koyanagi Y, Mitsuya H (2005) Potent Anti-R5-human immunodeficiency virus type 1 effects of a CCR5 antagonist, AK602/ONO4128/GW873140, in a novel human peripheral blood mononuclear cell nonobese diabetic-SCID, interleukin 2 receptor g-chain-knocked-out AIDS mouse model. J Virol 79: 2087–2096.

    Article  PubMed  CAS  Google Scholar 

  • Namikawa R, Kaneshima H, Lieberman M, Weissman IL, McCune JM (1988) Infection of the SCID-hu mouse by HIV-1. Science 242:1684–1686.

    Article  PubMed  CAS  Google Scholar 

  • Nimura F, Zhang LF, Okuma K, Tanaka R, Sunakawa H, Yamamoto N, Tanaka Y. (2006) Cross-linking cell surface chemokine receptors leads to isolation, activation, and differentiation of monocytes into potent dendritic cells. Exp Biol Med 231:431–443.

    CAS  Google Scholar 

  • Nonoyama S, Smith FO, Ochs HD (1993) Specific antibody production to a recall or a neoantigen by SCID mice reconstituted with human peripheral blood lymphocytes. J Immunol. 151:3894–3901.

    PubMed  CAS  Google Scholar 

  • Osame M, Usuku K, Izumo S, Ijichi N, Amitani H, Igata A, Matsumoto M, Tara M (1986) HTLV-I associated myelopathy, a new clinical entity. Lancet 1:1031–1032.

    Article  PubMed  CAS  Google Scholar 

  • Pastore C, Picchio GR, Galimi F, Fish R, Hartley O, Offord RE, Mosier DE (2003) Two mechanisms for human immunodeficiency virus type 1 inhibition by N-terminal modifications of RANTES. Antimicrob Agents Chemother 47:509–517.

    Article  PubMed  CAS  Google Scholar 

  • Peterson SR, Kurimasa A, Oshimura M, Dynan WS, Bradbury EM, Chen DJ (1995) Loss of the catalytic subunit of the DNA-dependent protein kinase in DNA double-strand-break-repair mutant mammalian cells. Proc Natl Acad Sci USA 92:3171–3174.

    Article  PubMed  CAS  Google Scholar 

  • Rabin L, Hincenbergs M, Moreno MB, Warren S, Linquist V, Datema R, Charpiot B, Seifert J, Kaneshima H, McCune J (1996) Use of standardized SCID/hu Thy/Liv mouse model for preclinical efficacy testing of anti-human immunodeficiency virus type 1 compounds. Antimicrob Agents Chemother 40:755–762.

    PubMed  CAS  Google Scholar 

  • Ruxrungtham K, Boone E, Ford H Jr, Driscoll JS, Davey RT Jr, Lane HC (1996) Potent activity of 2’-beta-fluoro-2’, 3’-dideoxyadenosine against human immunodeficiency virus type 1 infection in hu-PBL-SCID mice. Antimicrob Agents Chemother 40:2369–2374.

    PubMed  CAS  Google Scholar 

  • Sandhu JS, Gorczynski R, Shpitz B, Gallinger S, Nguyen HP, Hozumi N (1995) A human model of xenogeneic graft-versus-host disease in SCID mice engrafted with human peripheral blood lymphocytes. Transplantation 60:179–184.

    PubMed  CAS  Google Scholar 

  • Sandhu JS, Shpitz B, Gallinger S, Hozumi N (1994) Human primary immune response in SCID mice engrafted with human peripheral blood lymphocytes. J Immunol 152:3806–3813.

    PubMed  CAS  Google Scholar 

  • Santini S M, C Lapenta, M Logozzi, S Parlato, M Spada, T Di Pucchio, F Belardelli (2000) Type I interferon as a powerful adjuvant for monocyte-derived dendritic cell development and activity in vitro and in Hu-PBL-SCID mice. J Exp Med 191:1777–1788.

    Article  PubMed  CAS  Google Scholar 

  • Stanley SK, McCune JM, Kaneshima H, Justement JS, Sullivan M, Boone E, Baseler M, Adelsberger J, Bonyhadi M, Orenstein J et al. (1993) Human immunodeficiency virus infection of the human thymus and disruption of the thymic microenvironment in the SCID-hu mouse. J Exp Med 178:1151–1163.

    Article  PubMed  CAS  Google Scholar 

  • Strizki JM, Xu S, Wagner NE, Wojcik L, Liu J, Hou Y, Endres M, Palani A, Shapiro S, Clader JW, Greenlee WJ, Tagat JR, McCombie S, Cox K, Fawzi AB, Chou CC, Pugliese-Sivo C, Davies L, Moreno ME, Ho DD, Trkola A, Stoddart CA, Moore JP, Reyes GR, Baroudy BM (2001) SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infection in vitro and in vivo. Proc Natl Acad Sci USA 98:12718–12723.

    Article  PubMed  CAS  Google Scholar 

  • Tary-Lehmann M and Saxon A (1992) Human mature T cells that are anergic in vivo prevail in SCID mice reconstituted with human peripheral blood. J Exp Med 175:503–516.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Taylor GP, Matsuoka M (2005) Natural history of adult T-cell leukemia/lymphoma and approaches to therapy. Oncogene 24:6047–6057.

    Article  PubMed  CAS  Google Scholar 

  • Traggiai E, Chicha L, Mazzucchelli L, Bronz L, Piffaretti JC, Lanzavecchia A, Manz MG (2004) Development of a human adaptive immune system in cord blood cell-transplanted mice. Science 304:104–107.

    Article  PubMed  CAS  Google Scholar 

  • Uchiyama T, Hori T, Tsudo M, Wano Y, Umadome H, Tamori S, Yodoi J, Maeda M, Sawami H, Uchino H (1985) Interleukin-2 receptor (Tac antigen) expressed on adult T cell leukemia cells. J Clin Invest 76:446–453.

    Article  PubMed  CAS  Google Scholar 

  • Vandekerckhove BA, Namikawa R, Bacchetta R, Roncarolo MG (1992) Human hematopoietic cells and thymic epithelial cells induce tolerance via different mechanisms in the SCID-hu mouse thymus. J Exp Med 175:1033–1043.

    Article  PubMed  CAS  Google Scholar 

  • Watanabe S, Terashima K, Ohta S, Horibata S, Yajima M, Shiozawa Y, Dewan MZ, Yu Z, Ito M, Morio T, Shimizu N, Honda M, Yamamoto N (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 109:212–218.

    Article  PubMed  CAS  Google Scholar 

  • Yoshida A, Tanaka R, Kodama A, Yamamoto N, Ansari AA, Tanaka Y (2005) Identification of HIV-1 epitopes that induce the synthesis of a R5 HIV-1 suppression factor by human CD4+ T cells isolated from HIV-1 immunized hu-PBL SCID mice. Clin Dev Immunol 12:235–242.

    Article  PubMed  CAS  Google Scholar 

  • Yoshida A, Tanaka R, Murakam M, Takahashi T, Koyanagi Y, Nakamura M, Ito M, Yamamoto N, Tanaka Y (2003) Induction of protective immune responses against R5 HIV-1 infection in the hu-PBL-SCID mice by intra-splenic immunization with HIV-1-pulsed dendritic cells: possible involvement of a novel factor of human CD4+ T cell origin. J Virol 77:8719–8728.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute for Virus Research, Kyoto University, 606-8507, Kyoto, Japan

    Y. Koyanagi

  2. Department of Immunology, University of the Ryukyus, 903-0215, Okinawa, Japan

    Y. Tanaka

  3. Central Institute for Experimental Animals, 216-0001, Kawasaki, Japan

    M. Ito

  4. AIDS Research Center, National Institute of Infectious Diseases, 162-8640, Tokyo, Japan

    N. Yamamoto

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  1. Y. Koyanagi
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  2. Y. Tanaka
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  3. M. Ito
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  4. N. Yamamoto
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Editors and Affiliations

  1. Central Institute for Experimental Animals, 216-0001, Kawasaki, Japan

    Tatsuji Nomura M.D, Ph.D

  2. RIKEN, Yokohama, Japan

    Takeshi Watanabe M.D, Ph.D

  3. Tokai University School of Medicine, Kanagawa, Japan

    Sonoko Habu M.D, Ph.D

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Koyanagi, Y., Tanaka, Y., Ito, M., Yamamoto, N. (2008). Humanized Mice for Human Retrovirus Infection. In: Nomura, T., Watanabe, T., Habu, S. (eds) Humanized Mice. Current Topics in Microbiology and Immunology, vol 324. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-75647-7_9

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