Review article: Biomedical intelligence
Vol. 147 No. 4142 (2017)
Humanised mouse models for haematopoiesis and infectious diseases
- Veronika Lysenko
- Donal McHugh
- Lena Behrmann
- Mary-Aude Rochat
- Christian M. Wilk
- Larisa Kovtonyuk
- Jean-Pierre Bourquin
- Christian Münz
- Markus G. Manz
- Roberto Speck
- Alexandre P.A. Theocharides
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Cite this as:
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Swiss Med Wkly. 2017;147:w14516
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Published
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22.10.2017
Summary
“Humanised” mouse models have emerged over past years as powerful tools for investigating human haematopoiesis and immunity. They allowed the identification of key factors for the maintenance and function of normal and leukaemic human haematopoietic stem cells. These findings have been widely used to dissect the pathogenesis of multiple myeloid and lymphoid neoplasms, such as acute myeloid leukaemia and acute lymphoblastic leukaemia. Furthermore, these models can serve as a stepping-stone to clinical trials by testing novel drugs that target leukaemic stem cells. The investigation of human immunity in vivo is also of great interest in both the context of understanding the innate and adaptive immune system and responses to viral infections with exclusive human tropism, such as Epstein-Barr virus and human immunodeficiency virus. This review focuses on recent advances in the study of human haematopoiesis and immunity in humanised mouse models, underlining their relevance and limitations.
References
- Mestas J, Hughes CC. Of mice and not men: differences between mouse and human immunology. J Immunol. 2004;172(5):2731–8. doi:.https://doi.org/10.4049/jimmunol.172.5.2731
- Rongvaux A, Takizawa H, Strowig T, Willinger T, Eynon EE, Flavell RA, et al. Human hemato-lymphoid system mice: current use and future potential for medicine. Annu Rev Immunol. 2013;31(1):635–74. doi:.https://doi.org/10.1146/annurev-immunol-032712-095921
- Bosma GC, Custer RP, Bosma MJ. A severe combined immunodeficiency mutation in the mouse. Nature. 1983;301(5900):527–30. doi:.https://doi.org/10.1038/301527a0
- Mosier DE, Gulizia RJ, Baird SM, Wilson DB. Transfer of a functional human immune system to mice with severe combined immunodeficiency. Nature. 1988;335(6187):256–9. doi:.https://doi.org/10.1038/335256a0
- Lapidot T, Pflumio F, Doedens M, Murdoch B, Williams DE, Dick JE. Cytokine stimulation of multilineage hematopoiesis from immature human cells engrafted in SCID mice. Science. 1992;255(5048):1137–41. doi:.https://doi.org/10.1126/science.1372131
- Nonoyama S, Smith FO, Bernstein ID, Ochs HD. Strain-dependent leakiness of mice with severe combined immune deficiency. J Immunol. 1993;150(9):3817–24.
- Mombaerts P, Iacomini J, Johnson RS, Herrup K, Tonegawa S, Papaioannou VE. RAG-1-deficient mice have no mature B and T lymphocytes. Cell. 1992;68(5):869–77. doi:.https://doi.org/10.1016/0092-8674(92)90030-G
- Shultz LD, Schweitzer PA, Christianson SW, Gott B, Schweitzer IB, Tennent B, et al. Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice. J Immunol. 1995;154(1):180–91.
- Traggiai E, Chicha L, Mazzucchelli L, Bronz L, Piffaretti JC, Lanzavecchia A, et al. Development of a human adaptive immune system in cord blood cell-transplanted mice. Science. 2004;304(5667):104–7. doi:.https://doi.org/10.1126/science.1093933
- Kerre TC, De Smet G, De Smedt M, Zippelius A, Pittet MJ, Langerak AW, et al. Adapted NOD/SCID model supports development of phenotypically and functionally mature T cells from human umbilical cord blood CD34(+) cells. Blood. 2002;99(5):1620–6. doi:.https://doi.org/10.1182/blood.V99.5.1620
- Ito M, Hiramatsu H, Kobayashi K, Suzue K, Kawahata M, Hioki K, et al. NOD/SCID/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells. Blood. 2002;100(9):3175–82. doi:.https://doi.org/10.1182/blood-2001-12-0207
- Ishikawa F, Yasukawa M, Lyons B, Yoshida S, Miyamoto T, Yoshimoto G, et al. Development of functional human blood and immune systems in NOD/SCID/IL2 receptor gamma chain(null) mice. Blood. 2005;106(5):1565–73. doi:.https://doi.org/10.1182/blood-2005-02-0516
- Theocharides AP, Rongvaux A, Fritsch K, Flavell RA, Manz MG. Humanized hemato-lymphoid system mice. Haematologica. 2016;101(1):5–19. doi:.https://doi.org/10.3324/haematol.2014.115212
- Terpstra W, Leenen PJ, van den Bos C, Prins A, Loenen WA, Verstegen MM, et al. Facilitated engraftment of human hematopoietic cells in severe combined immunodeficient mice following a single injection of Cl2MDP liposomes. Leukemia. 1997;11(7):1049–54. doi:.https://doi.org/10.1038/sj.leu.2400694
- Takenaka K, Prasolava TK, Wang JC, Mortin-Toth SM, Khalouei S, Gan OI, et al. Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells. Nat Immunol. 2007;8(12):1313–23. doi:.https://doi.org/10.1038/ni1527
- Takizawa H, Manz MG. Macrophage tolerance: CD47-SIRP-alpha-mediated signals matter. Nat Immunol. 2007;8(12):1287–9. doi:.https://doi.org/10.1038/ni1207-1287
- Rongvaux A, Willinger T, Martinek J, Strowig T, Gearty SV, Teichmann LL, et al. Development and function of human innate immune cells in a humanized mouse model. Nat Biotechnol. 2014;32(4):364–72. doi:.https://doi.org/10.1038/nbt.2858
- Saito Y, Ellegast JM, Rafiei A, Song Y, Kull D, Heikenwalder M, et al. Peripheral blood CD34(+) cells efficiently engraft human cytokine knock-in mice. Blood. 2016;128(14):1829–33. doi:.https://doi.org/10.1182/blood-2015-10-676452
- Verma R, Strowig T, Das R, Koduru S, Hafemann A, Hopf S, et al. Humanized Mouse Model of Myeloma Reveals Clinically Occult Genomic Changes in Primary Tumor Cells. Blood. 2015;126(23).
- Das R, Strowig T, Verma R, Koduru S, Hafemann A, Hopf S, et al. Microenvironment-dependent growth of preneoplastic and malignant plasma cells in humanized mice. Nat Med. 2016;22(11):1351–7. doi:.https://doi.org/10.1038/nm.4202
- Cosgun KN, Rahmig S, Mende N, Reinke S, Hauber I, Schäfer C, et al. Kit regulates HSC engraftment across the human-mouse species barrier. Cell Stem Cell. 2014;15(2):227–38. doi:.https://doi.org/10.1016/j.stem.2014.06.001
- Notta F, Doulatov S, Laurenti E, Poeppl A, Jurisica I, Dick JE. Isolation of single human hematopoietic stem cells capable of long-term multilineage engraftment. Science. 2011;333(6039):218–21. doi:.https://doi.org/10.1126/science.1201219
- Laurenti E, Doulatov S, Zandi S, Plumb I, Chen J, April C, et al. The transcriptional architecture of early human hematopoiesis identifies multilevel control of lymphoid commitment. Nat Immunol. 2013;14(7):756–63. doi:.https://doi.org/10.1038/ni.2615
- Baum CM, Weissman IL, Tsukamoto AS, Buckle AM, Peault B. Isolation of a candidate human hematopoietic stem-cell population. Proc Natl Acad Sci USA. 1992;89(7):2804–8. doi:.https://doi.org/10.1073/pnas.89.7.2804
- Craig W, Kay R, Cutler RL, Lansdorp PM. Expression of Thy-1 on human hematopoietic progenitor cells. J Exp Med. 1993;177(5):1331–42. doi:.https://doi.org/10.1084/jem.177.5.1331
- Bhatia M, Wang JC, Kapp U, Bonnet D, Dick JE. Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice. Proc Natl Acad Sci USA. 1997;94(10):5320–5. doi:.https://doi.org/10.1073/pnas.94.10.5320
- Larochelle A, Vormoor J, Hanenberg H, Wang JC, Bhatia M, Lapidot T, et al. Identification of primitive human hematopoietic cells capable of repopulating NOD/SCID mouse bone marrow: implications for gene therapy. Nat Med. 1996;2(12):1329–37. doi:.https://doi.org/10.1038/nm1296-1329
- Kondo M, Wagers AJ, Manz MG, Prohaska SS, Scherer DC, Beilhack GF, et al. Biology of hematopoietic stem cells and progenitors: implications for clinical application. Annu Rev Immunol. 2003;21(1):759–806. doi:.https://doi.org/10.1146/annurev.immunol.21.120601.141007
- Majeti R, Park CY, Weissman IL. Identification of a hierarchy of multipotent hematopoietic progenitors in human cord blood. Cell Stem Cell. 2007;1(6):635–45. doi:.https://doi.org/10.1016/j.stem.2007.10.001
- McKenzie JL, Takenaka K, Gan OI, Doedens M, Dick JE. Low rhodamine 123 retention identifies long-term human hematopoietic stem cells within the Lin-CD34+CD38- population. Blood. 2007;109(2):543–5. doi:.https://doi.org/10.1182/blood-2006-06-030270
- Notta F, Zandi S, Takayama N, Dobson S, Gan OI, Wilson G, et al. Distinct routes of lineage development reshape the human blood hierarchy across ontogeny. Science. 2016;351(6269):aab2116. doi:.https://doi.org/10.1126/science.aab2116
- Yamamoto R, Morita Y, Ooehara J, Hamanaka S, Onodera M, Rudolph KL, et al. Clonal analysis unveils self-renewing lineage-restricted progenitors generated directly from hematopoietic stem cells. Cell. 2013;154(5):1112–26. doi:.https://doi.org/10.1016/j.cell.2013.08.007
- Catlin SN, Busque L, Gale RE, Guttorp P, Abkowitz JL. The replication rate of human hematopoietic stem cells in vivo. Blood. 2011;117(17):4460–6. doi:.https://doi.org/10.1182/blood-2010-08-303537
- Laurenti E, Frelin C, Xie S, Ferrari R, Dunant CF, Zandi S, et al. CDK6 levels regulate quiescence exit in human hematopoietic stem cells. Cell Stem Cell. 2015;16(3):302–13. doi:.https://doi.org/10.1016/j.stem.2015.01.017
- Rongvaux A, Willinger T, Takizawa H, Rathinam C, Auerbach W, Murphy AJ, et al. Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo. Proc Natl Acad Sci USA. 2011;108(6):2378–83. doi:.https://doi.org/10.1073/pnas.1019524108
- Strowig T, Rongvaux A, Rathinam C, Takizawa H, Borsotti C, Philbrick W, et al. Transgenic expression of human signal regulatory protein alpha in Rag2-/-gamma(c)-/- mice improves engraftment of human hematopoietic cells in humanized mice. Proc Natl Acad Sci USA. 2011;108(32):13218–23. doi:.https://doi.org/10.1073/pnas.1109769108
- Shlush LI, Zandi S, Mitchell A, Chen WC, Brandwein JM, Gupta V, et al.; HALT Pan-Leukemia Gene Panel Consortium. Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature. 2014;506(7488):328–33. doi:.https://doi.org/10.1038/nature13038
- Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367(6464):645–8. doi:.https://doi.org/10.1038/367645a0
- Hope KJ, Jin L, Dick JE. Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol. 2004;5(7):738–43. doi:.https://doi.org/10.1038/ni1080
- Thomas D, Majeti R. Biology and relevance of human acute myeloid leukemia stem cells. Blood. 2017;129(12):1577–85. doi:.https://doi.org/10.1182/blood-2016-10-696054
- Corces-Zimmerman MR, Hong WJ, Weissman IL, Medeiros BC, Majeti R. Preleukemic mutations in human acute myeloid leukemia affect epigenetic regulators and persist in remission. Proc Natl Acad Sci USA. 2014;111(7):2548–53. doi:.https://doi.org/10.1073/pnas.1324297111
- Townsend EC, Murakami MA, Christodoulou A, Christie AL, Köster J, DeSouza TA, et al. The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell. 2016;29(4):574–86. doi:.https://doi.org/10.1016/j.ccell.2016.03.008
- Theocharides AP, Jin L, Cheng PY, Prasolava TK, Malko AV, Ho JM, et al. Disruption of SIRPα signaling in macrophages eliminates human acute myeloid leukemia stem cells in xenografts. J Exp Med. 2012;209(10):1883–99. doi:.https://doi.org/10.1084/jem.20120502
- Majeti R, Chao MP, Alizadeh AA, Pang WW, Jaiswal S, Gibbs KD, Jr, et al. CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell. 2009;138(2):286–99. doi:.https://doi.org/10.1016/j.cell.2009.05.045
- Petrova PS, Viller NN, Wong M, Pang X, Lin GH, Dodge K, et al. TTI-621 (SIRPαFc): A CD47-Blocking Innate Immune Checkpoint Inhibitor with Broad Antitumor Activity and Minimal Erythrocyte Binding. Clin Cancer Res. 2017;23(4):1068–79. doi:.https://doi.org/10.1158/1078-0432.CCR-16-1700
- Ng SW, Mitchell A, Kennedy JA, Chen WC, McLeod J, Ibrahimova N, et al. A 17-gene stemness score for rapid determination of risk in acute leukaemia. Nature. 2016;540(7633):433–7. doi:.https://doi.org/10.1038/nature20598
- Ellegast JM, Rauch PJ, Kovtonyuk LV, Müller R, Wagner U, Saito Y, et al. inv(16) and NPM1mut AMLs engraft human cytokine knock-in mice. Blood. 2016;128(17):2130–4. doi:.https://doi.org/10.1182/blood-2015-12-689356
- Reinisch A, Thomas D, Corces MR, Zhang X, Gratzinger D, Hong WJ, et al. A humanized bone marrow ossicle xenotransplantation model enables improved engraftment of healthy and leukemic human hematopoietic cells. Nat Med. 2016;22(7):812–21. doi:.https://doi.org/10.1038/nm.4103
- Pang WW, Pluvinage JV, Price EA, Sridhar K, Arber DA, Greenberg PL, et al. Hematopoietic stem cell and progenitor cell mechanisms in myelodysplastic syndromes. Proc Natl Acad Sci USA. 2013;110(8):3011–6. doi:.https://doi.org/10.1073/pnas.1222861110
- Woll PS, Kjällquist U, Chowdhury O, Doolittle H, Wedge DC, Thongjuea S, et al. Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo. Cancer Cell. 2014;25(6):794–808. doi:.. Correction in: Cancer Cell. 2015;27(4)603–5. http://www.cell.com/cancer-cell/fulltext/S1535-6108(15)00091-4 https://doi.org/10.1016/j.ccr.2014.03.036
- Medyouf H, Mossner M, Jann JC, Nolte F, Raffel S, Herrmann C, et al. Myelodysplastic cells in patients reprogram mesenchymal stromal cells to establish a transplantable stem cell niche disease unit. Cell Stem Cell. 2014;14(6):824–37. doi:.https://doi.org/10.1016/j.stem.2014.02.014
- Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011;117(19):5019–32. doi:.https://doi.org/10.1182/blood-2011-01-293050
- Dores GM, Devesa SS, Curtis RE, Linet MS, Morton LM. Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007. Blood. 2012;119(1):34–43. doi:.https://doi.org/10.1182/blood-2011-04-347872
- Liem NL, Papa RA, Milross CG, Schmid MA, Tajbakhsh M, Choi S, et al. Characterization of childhood acute lymphoblastic leukemia xenograft models for the preclinical evaluation of new therapies. Blood. 2004;103(10):3905–14. doi:.https://doi.org/10.1182/blood-2003-08-2911
- Jones L, Carol H, Evans K, Richmond J, Houghton PJ, Smith MA, et al. A review of new agents evaluated against pediatric acute lymphoblastic leukemia by the Pediatric Preclinical Testing Program. Leukemia. 2016;30(11):2133–41. doi:.https://doi.org/10.1038/leu.2016.192
- Imada K. Immunodeficient mouse models of lymphoid tumors. Int J Hematol. 2003;77(4):336–41. doi:.https://doi.org/10.1007/BF02982640
- Shultz LD, Lyons BL, Burzenski LM, Gott B, Chen X, Chaleff S, et al. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J Immunol. 2005;174(10):6477–89. doi:.https://doi.org/10.4049/jimmunol.174.10.6477
- Agliano A, Martin-Padura I, Mancuso P, Marighetti P, Rabascio C, Pruneri G, et al. Human acute leukemia cells injected in NOD/LtSz-scid/IL-2Rgamma null mice generate a faster and more efficient disease compared to other NOD/scid-related strains. Int J Cancer. 2008;123(9):2222–7. doi:.https://doi.org/10.1002/ijc.23772
- le Viseur C, Hotfilder M, Bomken S, Wilson K, Röttgers S, Schrauder A, et al. In childhood acute lymphoblastic leukemia, blasts at different stages of immunophenotypic maturation have stem cell properties. Cancer Cell. 2008;14(1):47–58. doi:.https://doi.org/10.1016/j.ccr.2008.05.015
- Schmitz M, Breithaupt P, Scheidegger N, Cario G, Bonapace L, Meissner B, et al. Xenografts of highly resistant leukemia recapitulate the clonal composition of the leukemogenic compartment. Blood. 2011;118(7):1854–64. doi:.https://doi.org/10.1182/blood-2010-11-320309
- Ebinger S, Özdemir EZ, Ziegenhain C, Tiedt S, Castro Alves C, Grunert M, et al. Characterization of Rare, Dormant, and Therapy-Resistant Cells in Acute Lymphoblastic Leukemia. Cancer Cell. 2016;30(6):849–62. doi:.https://doi.org/10.1016/j.ccell.2016.11.002
- Rehe K, Wilson K, Bomken S, Williamson D, Irving J, den Boer ML, et al. Acute B lymphoblastic leukaemia-propagating cells are present at high frequency in diverse lymphoblast populations. EMBO Mol Med. 2013;5(1):38–51. doi:.https://doi.org/10.1002/emmm.201201703
- Clappier E, Gerby B, Sigaux F, Delord M, Touzri F, Hernandez L, et al. Clonal selection in xenografted human T cell acute lymphoblastic leukemia recapitulates gain of malignancy at relapse. J Exp Med. 2011;208(4):653–61. doi:.https://doi.org/10.1084/jem.20110105
- Fischer U, Forster M, Rinaldi A, Risch T, Sungalee S, Warnatz HJ, et al. Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options. Nat Genet. 2015;47(9):1020–9. doi:.https://doi.org/10.1038/ng.3362
- Barabé F, Kennedy JA, Hope KJ, Dick JE. Modeling the initiation and progression of human acute leukemia in mice. Science. 2007;316(5824):600–4. doi:.https://doi.org/10.1126/science.1139851
- Lin S, Luo RT, Ptasinska A, Kerry J, Assi SA, Wunderlich M, et al. Instructive Role of MLL-Fusion Proteins Revealed by a Model of t(4;11) Pro-B Acute Lymphoblastic Leukemia. Cancer Cell. 2016;30(5):737–49. doi:.https://doi.org/10.1016/j.ccell.2016.10.008
- Notta F, Mullighan CG, Wang JC, Poeppl A, Doulatov S, Phillips LA, et al. Evolution of human BCR-ABL1 lymphoblastic leukaemia-initiating cells. Nature. 2011;469(7330):362–7. doi:.https://doi.org/10.1038/nature09733
- Frismantas V, Dobay MP, Rinaldi A, Tchinda J, Dunn SH, Kunz J, et al. Ex vivo drug response profiling detects recurrent sensitivity patterns in drug resistant ALL. Blood. 2017; 129(11):e26–37. doi:.https://doi.org/10.1182/blood-2016-09-738070
- Patel B, Dey A, Castleton AZ, Schwab C, Samuel E, Sivakumaran J, et al. Mouse xenograft modeling of human adult acute lymphoblastic leukemia provides mechanistic insights into adult LIC biology. Blood. 2014;124(1):96–105. doi:.https://doi.org/10.1182/blood-2014-01-549352
- Macor P, Secco E, Zorzet S, Tripodo C, Celeghini C, Tedesco F. An update on the xenograft and mouse models suitable for investigating new therapeutic compounds for the treatment of B-cell malignancies. Curr Pharm Des. 2008;14(21):2023–39. doi:.https://doi.org/10.2174/138161208785294591
- Donnou S, Galand C, Touitou V, Sautès-Fridman C, Fabry Z, Fisson S. Murine models of B-cell lymphomas: promising tools for designing cancer therapies. Adv Hematol. 2012;2012:701704. doi:.https://doi.org/10.1155/2012/701704
- Birkenmeier K, Moll K, Newrzela S, Hartmann S, Dröse S, Hansmann ML. Basal autophagy is pivotal for Hodgkin and Reed-Sternberg cells’ survival and growth revealing a new strategy for Hodgkin lymphoma treatment. Oncotarget. 2016;7(29):46579–88. doi:.https://doi.org/10.18632/oncotarget.10300
- Chu Y, Hochberg J, Yahr A, Ayello J, van de Ven C, Barth M, et al. Targeting CD20+ Aggressive B-cell Non-Hodgkin Lymphoma by Anti-CD20 CAR mRNA-Modified Expanded Natural Killer Cells In Vitro and in NSG Mice. Cancer Immunol Res. 2015;3(4):333–44. doi:.https://doi.org/10.1158/2326-6066.CIR-14-0114
- Deutsch AJA, Rinner B, Pichler M, Prochazka K, Pansy K, Bischof M, et al. NR4A3 suppresses lymphomagenesis through induction of proapoptotic genes. Cancer Res. 2017;77(9):2375–86. doi:.https://doi.org/10.1158/0008-5472.CAN-16-2320
- Suryani S, Carol H, Chonghaile TN, Frismantas V, Sarmah C, High L, et al. Cell and molecular determinants of in vivo efficacy of the BH3 mimetic ABT-263 against pediatric acute lymphoblastic leukemia xenografts. Clin Cancer Res. 2014;20(17):4520–31. doi:.https://doi.org/10.1158/1078-0432.CCR-14-0259
- Bonapace L, Bornhauser BC, Schmitz M, Cario G, Ziegler U, Niggli FK, et al. Induction of autophagy-dependent necroptosis is required for childhood acute lymphoblastic leukemia cells to overcome glucocorticoid resistance. J Clin Invest. 2010;120(4):1310–23. doi:.https://doi.org/10.1172/JCI39987
- McComb S, Aguadé-Gorgorió J, Harder L, Marovca B, Cario G, Eckert C, et al. Activation of concurrent apoptosis and necroptosis by SMAC mimetics for the treatment of refractory and relapsed ALL. Sci Transl Med. 2016;8(339):339ra70. doi:.https://doi.org/10.1126/scitranslmed.aad2986
- Hawkins ED, Duarte D, Akinduro O, Khorshed RA, Passaro D, Nowicka M, et al. T-cell acute leukaemia exhibits dynamic interactions with bone marrow microenvironments. Nature. 2016;538(7626):518–22. doi:.https://doi.org/10.1038/nature19801
- Herman SE, Wiestner A. Preclinical modeling of novel therapeutics in chronic lymphocytic leukemia: the tools of the trade. Semin Oncol. 2016;43(2):222–32. doi:.https://doi.org/10.1053/j.seminoncol.2016.02.007
- Strowig T, Gurer C, Ploss A, Liu YF, Arrey F, Sashihara J, et al. Priming of protective T cell responses against virus-induced tumors in mice with human immune system components. J Exp Med. 2009;206(6):1423–34. doi:.https://doi.org/10.1084/jem.20081720
- Strowig T, Chijioke O, Carrega P, Arrey F, Meixlsperger S, Rämer PC, et al. Human NK cells of mice with reconstituted human immune system components require preactivation to acquire functional competence. Blood. 2010;116(20):4158–67. doi:.https://doi.org/10.1182/blood-2010-02-270678
- Salguero G, Daenthanasanmak A, Münz C, Raykova A, Guzmán CA, Riese P, et al. Dendritic cell-mediated immune humanization of mice: implications for allogeneic and xenogeneic stem cell transplantation. J Immunol. 2014;192(10):4636–47. doi:.https://doi.org/10.4049/jimmunol.1302887
- Landtwing V, Raykova A, Pezzino G, Béziat V, Marcenaro E, Graf C, et al. Cognate HLA absence in trans diminishes human NK cell education. J Clin Invest. 2016;126(10):3772–82. doi:.https://doi.org/10.1172/JCI86923
- Nochi T, Denton PW, Wahl A, Garcia JV. Cryptopatches are essential for the development of human GALT. Cell Reports. 2013;3(6):1874–84. doi:.https://doi.org/10.1016/j.celrep.2013.05.037
- Meixlsperger S, Leung CS, Rämer PC, Pack M, Vanoaica LD, Breton G, et al. CD141+ dendritic cells produce prominent amounts of IFN-α after dsRNA recognition and can be targeted via DEC-205 in humanized mice. Blood. 2013;121(25):5034–44. doi:.https://doi.org/10.1182/blood-2012-12-473413
- Ishikawa F, Niiro H, Iino T, Yoshida S, Saito N, Onohara S, et al. The developmental program of human dendritic cells is operated independently of conventional myeloid and lymphoid pathways. Blood. 2007;110(10):3591–660. doi:.https://doi.org/10.1182/blood-2007-02-071613
- Ding Y, Wilkinson A, Idris A, Fancke B, O’Keeffe M, Khalil D, et al. FLT3-ligand treatment of humanized mice results in the generation of large numbers of CD141+ and CD1c+ dendritic cells in vivo. J Immunol. 2014;192(4):1982–9. doi:.https://doi.org/10.4049/jimmunol.1302391
- Gurer C, Strowig T, Brilot F, Pack M, Trumpfheller C, Arrey F, et al. Targeting the nuclear antigen 1 of Epstein-Barr virus to the human endocytic receptor DEC-205 stimulates protective T-cell responses. Blood. 2008;112(4):1231–9. doi:.https://doi.org/10.1182/blood-2008-03-148072
- Yajima M, Imadome K, Nakagawa A, Watanabe S, Terashima K, Nakamura H, et al. T cell-mediated control of Epstein-Barr virus infection in humanized mice. J Infect Dis. 2009;200(10):1611–5. Published online October 17, 2009. doi:.https://doi.org/10.1086/644644
- Shultz LD, Saito Y, Najima Y, Tanaka S, Ochi T, Tomizawa M, et al. Generation of functional human T-cell subsets with HLA-restricted immune responses in HLA class I expressing NOD/SCID/IL2r gamma(null) humanized mice. Proc Natl Acad Sci USA. 2010;107(29):13022–7. doi:.https://doi.org/10.1073/pnas.1000475107
- Antsiferova O, Müller A, Rämer PC, Chijioke O, Chatterjee B, Raykova A, et al. Adoptive transfer of EBV specific CD8+ T cell clones can transiently control EBV infection in humanized mice. PLoS Pathog. 2014;10(8):e1004333. doi:.https://doi.org/10.1371/journal.ppat.1004333
- Gorantla S, Makarov E, Finke-Dwyer J, Gebhart CL, Domm W, Dewhurst S, et al. CD8+ cell depletion accelerates HIV-1 immunopathology in humanized mice. J Immunol. 2010;184(12):7082–91. doi:.https://doi.org/10.4049/jimmunol.1000438
- Billerbeck E, Horwitz JA, Labitt RN, Donovan BM, Vega K, Budell WC, et al. Characterization of human antiviral adaptive immune responses during hepatotropic virus infection in HLA-transgenic human immune system mice. J Immunol. 2013;191(4):1753–64. doi:.https://doi.org/10.4049/jimmunol.1201518
- Chijioke O, Marcenaro E, Moretta A, Capaul R, Munz C. Role of the 2B4 Receptor in CD8+ T-Cell-Dependent Immune Control of Epstein-Barr Virus Infection in Mice With Reconstituted Human Immune System Components. J Infect Dis. 2015;212(5):803–7. doi:. https://doi.org/10.1093/infdis/jiv114
- Chijioke O, Müller A, Feederle R, Barros MH, Krieg C, Emmel V, et al. Human natural killer cells prevent infectious mononucleosis features by targeting lytic Epstein-Barr virus infection. Cell Reports. 2013;5(6):1489–98. Published online December 24, 2013. doi:.. Correction published in: Cell Reports. 2015;12(5):901. https://doi.org/10.1016/j.celrep.2013.11.041
- Jandus C, Boligan KF, Chijioke O, Liu H, Dahlhaus M, Démoulins T, et al. Interactions between Siglec-7/9 receptors and ligands influence NK cell-dependent tumor immunosurveillance. J Clin Invest. 2014;124(4):1810–20. doi:.https://doi.org/10.1172/JCI65899
- Baenziger S, Tussiwand R, Schlaepfer E, Mazzucchelli L, Heikenwalder M, Kurrer MO, et al. Disseminated and sustained HIV infection in CD34+ cord blood cell-transplanted Rag2-/-gamma c-/- mice. Proc Natl Acad Sci USA. 2006;103(43):15951–6. doi:.https://doi.org/10.1073/pnas.0604493103
- Willinger T, Rongvaux A, Takizawa H, Yancopoulos GD, Valenzuela DM, Murphy AJ, et al. Human IL-3/GM-CSF knock-in mice support human alveolar macrophage development and human immune responses in the lung. Proc Natl Acad Sci USA. 2011;108(6):2390–5. doi:.https://doi.org/10.1073/pnas.1019682108
- Yu CI, Becker C, Wang Y, Marches F, Helft J, Leboeuf M, et al. Human CD1c+ dendritic cells drive the differentiation of CD103+ CD8+ mucosal effector T cells via the cytokine TGF-β. Immunity. 2013;38(4):818–30. doi:.https://doi.org/10.1016/j.immuni.2013.03.004
- Heuts F, Gavier-Widén D, Carow B, Juarez J, Wigzell H, Rottenberg ME. CD4+ cell-dependent granuloma formation in humanized mice infected with mycobacteria. Proc Natl Acad Sci USA. 2013;110(16):6482–7. doi:.https://doi.org/10.1073/pnas.1219985110
- Billerbeck E, Barry WT, Mu K, Dorner M, Rice CM, Ploss A. Development of human CD4+FoxP3+ regulatory T cells in human stem cell factor-, granulocyte-macrophage colony-stimulating factor-, and interleukin-3-expressing NOD-SCID IL2Rγ(null) humanized mice. Blood. 2011;117(11):3076–86. doi:.https://doi.org/10.1182/blood-2010-08-301507
- Wang F. Nonhuman primate models for Epstein-Barr virus infection. Curr Opin Virol. 2013;3(3):233–7. doi:.https://doi.org/10.1016/j.coviro.2013.03.003
- Epstein MA, Achong BG, Barr YM. Virus Particles in Cultured Lymphoblasts from Burkitt’s Lymphoma. Lancet. 1964;1(7335):702–3. doi:.https://doi.org/10.1016/S0140-6736(64)91524-7
- Yajima M, Imadome K, Nakagawa A, Watanabe S, Terashima K, Nakamura H, et al. A new humanized mouse model of Epstein-Barr virus infection that reproduces persistent infection, lymphoproliferative disorder, and cell-mediated and humoral immune responses. J Infect Dis. 2008;198(5):673–82. doi:.https://doi.org/10.1086/590502
- Tsai MH, Raykova A, Klinke O, Bernhardt K, Gärtner K, Leung CS, et al. Spontaneous lytic replication and epitheliotropism define an Epstein-Barr virus strain found in carcinomas. Cell Reports. 2013;5(2):458–70. doi:.https://doi.org/10.1016/j.celrep.2013.09.012
- Cocco M, Bellan C, Tussiwand R, Corti D, Traggiai E, Lazzi S, et al. CD34+ cord blood cell-transplanted Rag2-/- gamma(c)-/- mice as a model for Epstein-Barr virus infection. Am J Pathol. 2008;173(5):1369–78. doi:.https://doi.org/10.2353/ajpath.2008.071186
- Ma SD, Hegde S, Young KH, Sullivan R, Rajesh D, Zhou Y, et al. A new model of Epstein-Barr virus infection reveals an important role for early lytic viral protein expression in the development of lymphomas. J Virol. 2011;85(1):165–77. doi:.https://doi.org/10.1128/JVI.01512-10
- Heuts F, Rottenberg ME, Salamon D, Rasul E, Adori M, Klein G, et al. T cells modulate Epstein-Barr virus latency phenotypes during infection of humanized mice. J Virol. 2014;88(6):3235–45. doi:.https://doi.org/10.1128/JVI.02885-13
- Azzi T, Lünemann A, Murer A, Ueda S, Béziat V, Malmberg KJ, et al. Role for early-differentiated natural killer cells in infectious mononucleosis. Blood. 2014;124(16):2533–43. doi:.https://doi.org/10.1182/blood-2014-01-553024
- Gurer C, Strowig T, Brilot F, Pack M, Trumpfheller C, Arrey F, et al. Targeting the nuclear antigen 1 of Epstein-Barr virus to the human endocytic receptor DEC-205 stimulates protective T-cell responses. Blood. 2008;112(4):1231–9. doi:.https://doi.org/10.1182/blood-2008-03-148072
- White RE, Rämer PC, Naresh KN, Meixlsperger S, Pinaud L, Rooney C, et al. EBNA3B-deficient EBV promotes B cell lymphomagenesis in humanized mice and is found in human tumors. J Clin Invest. 2012;122(4):1487–502. Published online March 13, 2012. doi:.https://doi.org/10.1172/JCI58092
- Clapham PR, McKnight A. Cell surface receptors, virus entry and tropism of primate lentiviruses. J Gen Virol. 2002;83(Pt 8):1809–29. doi:.https://doi.org/10.1099/0022-1317-83-8-1809
- Gifford RJ. Viral evolution in deep time: lentiviruses and mammals. Trends Genet. 2012;28(2):89–100. doi:.https://doi.org/10.1016/j.tig.2011.11.003
- Goff SP. Intracellular trafficking of retroviral genomes during the early phase of infection: viral exploitation of cellular pathways. J Gene Med. 2001;3(6):517–28. doi:.https://doi.org/10.1002/1521-2254(200111)3:6<517::AID-JGM234>3.0.CO;2-E
- Boeke JD, Stoye JP. Retrotransposons, Endogenous Retroviruses, and the Evolution of Retroelements. In: Coffin JM, Hughes SH, Varmus HE, editors. Retroviruses. Cold Spring Harbor (NY): 1997.
- Doitsh G, Greene WC. Dissecting How CD4 T Cells Are Lost During HIV Infection. Cell Host Microbe. 2016;19(3):280–91. doi:.https://doi.org/10.1016/j.chom.2016.02.012
- Nasi M, Pinti M, Mussini C, Cossarizza A. Persistent inflammation in HIV infection: established concepts, new perspectives. Immunol Lett. 2014;161(2):184–8. doi:.https://doi.org/10.1016/j.imlet.2014.01.008
- Moir S, Fauci AS. B-cell exhaustion in HIV infection: the role of immune activation. Curr Opin HIV AIDS. 2014;9(5):472–7. doi:.https://doi.org/10.1097/COH.0000000000000092
- Seddiki N, Brezar V, Draenert R. Cell exhaustion in HIV-1 infection: role of suppressor cells. Curr Opin HIV AIDS. 2014;9(5):452–8. doi:.https://doi.org/10.1097/COH.0000000000000087
- Sagar M. Origin of the transmitted virus in HIV infection: infected cells versus cell-free virus. J Infect Dis. 2014;210(Suppl 3):S667–73. doi:.https://doi.org/10.1093/infdis/jiu369
- Battistini A, Sgarbanti M. HIV-1 latency: an update of molecular mechanisms and therapeutic strategies. Viruses. 2014;6(4):1715–58. doi:.https://doi.org/10.3390/v6041715
- Mbonye U, Karn J. Transcriptional control of HIV latency: cellular signaling pathways, epigenetics, happenstance and the hope for a cure. Virology. 2014;454-455:328–39. doi:.https://doi.org/10.1016/j.virol.2014.02.008
- Churchill MJ, Deeks SG, Margolis DM, Siliciano RF, Swanstrom R. HIV reservoirs: what, where and how to target them. Nat Rev Microbiol. 2016;14(1):55–60. doi:.https://doi.org/10.1038/nrmicro.2015.5
- Fois AF, Brew BJ. The Potential of the CNS as a Reservoir for HIV-1 Infection: Implications for HIV Eradication. Curr HIV/AIDS Rep. 2015;12(2):299–303. doi:.https://doi.org/10.1007/s11904-015-0257-9
- Kandathil AJ, Sugawara S, Balagopal A. Are T cells the only HIV-1 reservoir? Retrovirology. 2016;13(1):86. doi:.. Correction published in: Retrovirology. 2017;14:11. https://doi.org/10.1186/s12977-016-0323-4
- Giri MS, Nebozhyn M, Showe L, Montaner LJ. Microarray data on gene modulation by HIV-1 in immune cells: 2000-2006. J Leukoc Biol. 2006;80(5):1031–43. doi:.https://doi.org/10.1189/jlb.0306157
- Younas M, Psomas C, Reynes J, Corbeau P. Immune activation in the course of HIV-1 infection: Causes, phenotypes and persistence under therapy. HIV Med. 2016;17(2):89–105. doi:.https://doi.org/10.1111/hiv.12310
- Pawlowski A, Jansson M, Sköld M, Rottenberg ME, Källenius G. Tuberculosis and HIV co-infection. PLoS Pathog. 2012;8(2):e1002464. doi:.https://doi.org/10.1371/journal.ppat.1002464
- Desai DV, Kulkarni SS. Herpes Simplex Virus: The Interplay Between HSV, Host, and HIV-1. Viral Immunol. 2015;28(10):546–55. doi:.https://doi.org/10.1089/vim.2015.0012
- Carbone A, Gloghini A, Caruso A, De Paoli P, Dolcetti R. The impact of EBV and HIV infection on the microenvironmental niche underlying Hodgkin lymphoma pathogenesis. Int J Cancer. 2017;140(6):1233–45. doi:.https://doi.org/10.1002/ijc.30473
- Kuritzkes DR. Hematopoietic stem cell transplantation for HIV cure. J Clin Invest. 2016;126(2):432–7. doi:.https://doi.org/10.1172/JCI80563
- Wang HB, Mo QH, Yang Z. HIV vaccine research: the challenge and the way forward. J Immunol Res. 2015;2015:503978. doi:.https://doi.org/10.1155/2015/503978
- Brockman MA, Jones RB, Brumme ZL. Challenges and Opportunities for T-Cell-Mediated Strategies to Eliminate HIV Reservoirs. Front Immunol. 2015;6:506. doi:.https://doi.org/10.3389/fimmu.2015.00506
- Shang HT, Ding JW, Yu SY, Wu T, Zhang QL, Liang FJ. Progress and challenges in the use of latent HIV-1 reactivating agents. Acta Pharmacol Sin. 2015;36(8):908–16. doi:.https://doi.org/10.1038/aps.2015.22
- Chun TW, Stuyver L, Mizell SB, Ehler LA, Mican JA, Baseler M, et al. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci USA. 1997;94(24):13193–7. doi:.https://doi.org/10.1073/pnas.94.24.13193
- Finzi D, Blankson J, Siliciano JD, Margolick JB, Chadwick K, Pierson T, et al. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat Med. 1999;5(5):512–7. doi:.https://doi.org/10.1038/8394
- McCune JM. The SCID-hu mouse: a small animal model for the analysis of human hematolymphoid differentiation and function. Bone Marrow Transplant. 1992;9(Suppl 1):74–6.
- Namikawa R, Weilbaecher KN, Kaneshima H, Yee EJ, McCune JM. Long-term human hematopoiesis in the SCID-hu mouse. J Exp Med. 1990;172(4):1055–63. doi:.https://doi.org/10.1084/jem.172.4.1055
- McCune JM, Namikawa R, Shih CC, Rabin L, Kaneshima H. Suppression of HIV infection in AZT-treated SCID-hu mice. Science. 1990;247(4942):564–6. doi:.https://doi.org/10.1126/science.2300816
- Shih CC, Kaneshima H, Rabin L, Namikawa R, Sager P, McGowan J, et al. Postexposure prophylaxis with zidovudine suppresses human immunodeficiency virus type 1 infection in SCID-hu mice in a time-dependent manner. J Infect Dis. 1991;163(3):625–7. doi:.https://doi.org/10.1093/infdis/163.3.625
- Stoddart CA, Bales CA, Bare JC, Chkhenkeli G, Galkina SA, Kinkade AN, et al. Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals. PLoS One. 2007;2(7):e655. doi:.https://doi.org/10.1371/journal.pone.0000655
- Pettoello-Mantovani M, Kollmann TR, Raker C, Kim A, Yurasov S, Tudor R, et al. Saquinavir-mediated inhibition of human immunodeficiency virus (HIV) infection in SCID mice implanted with human fetal thymus and liver tissue: an in vivo model for evaluating the effect of drug therapy on HIV infection in lymphoid tissues. Antimicrob Agents Chemother. 1997;41(9):1880–7.
- Berges BK, Wheat WH, Palmer BE, Connick E, Akkina R. HIV-1 infection and CD4 T cell depletion in the humanized Rag2-/-gamma c-/- (RAG-hu) mouse model. Retrovirology. 2006;3(1):76. doi:.https://doi.org/10.1186/1742-4690-3-76
- Watanabe S, Terashima K, Ohta S, Horibata S, Yajima M, Shiozawa Y, et al. 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. 2007;109(1):212–8. doi:.https://doi.org/10.1182/blood-2006-04-017681
- Zhang L, Kovalev GI, Su L. HIV-1 infection and pathogenesis in a novel humanized mouse model. Blood. 2007;109(7):2978–81. doi:.https://doi.org/10.1182/blood-2006-07-033159
- Araínga M, Su H, Poluektova LY, Gorantla S, Gendelman HE. HIV-1 cellular and tissue replication patterns in infected humanized mice. Sci Rep. 2016;6(1):23513. doi:.https://doi.org/10.1038/srep23513
- Berges BK, Rowan MR. The utility of the new generation of humanized mice to study HIV-1 infection: transmission, prevention, pathogenesis, and treatment. Retrovirology. 2011;8(1):65. doi:.https://doi.org/10.1186/1742-4690-8-65
- Choudhary SK, Archin NM, Cheema M, Dahl NP, Garcia JV, Margolis DM. Latent HIV-1 infection of resting CD4+ T cells in the humanized Rag2−/− γc−/− mouse. J Virol. 2012;86(1):114–20. doi:.https://doi.org/10.1128/JVI.05590-11
- Kim KC, Choi BS, Kim KC, Park KH, Lee HJ, Cho YK, et al. A Simple Mouse Model for the Study of Human Immunodeficiency Virus. AIDS Res Hum Retroviruses. 2016;32(2):194–202. doi:.https://doi.org/10.1089/aid.2015.0211
- Metcalf Pate KA, Pohlmeyer CW, Walker-Sperling VE, Foote JB, Najarro KM, Cryer CG, et al. A Murine Viral Outgrowth Assay to Detect Residual HIV Type 1 in Patients With Undetectable Viral Loads. J Infect Dis. 2015;212(9):1387–96. doi:.https://doi.org/10.1093/infdis/jiv230
- Konadu KA, Anderson JS, Huang MB, Ali SA, Powell MD, Villinger F, et al. Hallmarks of HIV-1 pathogenesis are modulated by Nef’s Secretion Modification Region. J AIDS Clin Res. 2015;6(7):476. doi:.https://doi.org/10.4172/2155-6113.1000476
- Sampey GC, Saifuddin M, Schwab A, Barclay R, Punya S, Chung MC, et al. Exosomes from HIV-1-infected Cells Stimulate Production of Pro-inflammatory Cytokines through Trans-activating Response (TAR) RNA. J Biol Chem. 2016;291(3):1251–66. doi:.https://doi.org/10.1074/jbc.M115.662171
- Neff CP, Ndolo T, Tandon A, Habu Y, Akkina R. Oral pre-exposure prophylaxis by anti-retrovirals raltegravir and maraviroc protects against HIV-1 vaginal transmission in a humanized mouse model. PLoS One. 2010;5(12):e15257. doi:.https://doi.org/10.1371/journal.pone.0015257
- Mandal S, Prathipati PK, Kang G, Zhou Y, Yuan Z, Fan W, et al. Tenofovir alafenamide and elvitegravir loaded nanoparticles for long-acting prevention of HIV-1 vaginal transmission. AIDS. 2017;31(4):469–76. doi:.https://doi.org/10.1097/QAD.0000000000001349
- Campos N, Myburgh R, Garcel A, Vautrin A, Lapasset L, Nadal ES, et al. Long lasting control of viral rebound with a new drug ABX464 targeting Rev - mediated viral RNA biogenesis. Retrovirology. 2015;12(1):30. doi:.https://doi.org/10.1186/s12977-015-0159-3
- Nischang M, Sutmuller R, Gers-Huber G, Audigé A, Li D, Rochat MA, et al. Humanized mice recapitulate key features of HIV-1 infection: a novel concept using long-acting anti-retroviral drugs for treating HIV-1. PLoS One. 2012;7(6):e38853. doi:.https://doi.org/10.1371/journal.pone.0038853
- Dash PK, Gendelman HE, Roy U, Balkundi S, Alnouti Y, Mosley RL, et al. Long-acting nanoformulated antiretroviral therapy elicits potent antiretroviral and neuroprotective responses in HIV-1-infected humanized mice. AIDS. 2012;26(17):2135–44. doi:.https://doi.org/10.1097/QAD.0b013e328357f5ad
- Gnanadhas DP, Dash PK, Sillman B, Bade AN, Lin Z, Palandri DL, et al. Autophagy facilitates macrophage depots of sustained-release nanoformulated antiretroviral drugs. J Clin Invest. 2017;127(3):857–73. doi:.https://doi.org/10.1172/JCI90025
- Pardi N, Secreto AJ, Shan X, Debonera F, Glover J, Yi Y, et al. Administration of nucleoside-modified mRNA encoding broadly neutralizing antibody protects humanized mice from HIV-1 challenge. Nat Commun. 2017;8:14630. doi:.https://doi.org/10.1038/ncomms14630
- Lu CL, Murakowski DK, Bournazos S, Schoofs T, Sarkar D, Halper-Stromberg A, et al. Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo. Science. 2016;352(6288):1001–4. doi:.https://doi.org/10.1126/science.aaf1279
- Halper-Stromberg A, Lu CL, Klein F, Horwitz JA, Bournazos S, Nogueira L, et al. Broadly neutralizing antibodies and viral inducers decrease rebound from HIV-1 latent reservoirs in humanized mice. Cell. 2014;158(5):989–99. doi:.https://doi.org/10.1016/j.cell.2014.07.043
- Lan P, Tonomura N, Shimizu A, Wang S, Yang YG. Reconstitution of a functional human immune system in immunodeficient mice through combined human fetal thymus/liver and CD34+ cell transplantation. Blood. 2006;108(2):487–92. doi:.https://doi.org/10.1182/blood-2005-11-4388
- Brainard DM, Seung E, Frahm N, Cariappa A, Bailey CC, Hart WK, et al. Induction of robust cellular and humoral virus-specific adaptive immune responses in human immunodeficiency virus-infected humanized BLT mice. J Virol. 2009;83(14):7305–21. doi:.https://doi.org/10.1128/JVI.02207-08
- Dudek TE, No DC, Seung E, Vrbanac VD, Fadda L, Bhoumik P, et al. Rapid evolution of HIV-1 to functional CD8+ T cell responses in humanized BLT mice. Sci Transl Med. 2012;4(143):143ra98. doi:.https://doi.org/10.1126/scitranslmed.3003984
- Hofer U, Baenziger S, Heikenwalder M, Schlaepfer E, Gehre N, Regenass S, et al. RAG2-/- gamma(c)-/- mice transplanted with CD34+ cells from human cord blood show low levels of intestinal engraftment and are resistant to rectal transmission of human immunodeficiency virus. J Virol. 2008;82(24):12145–53. doi:.https://doi.org/10.1128/JVI.01105-08
- Sun Z, Denton PW, Estes JD, Othieno FA, Wei BL, Wege AK, et al. Intrarectal transmission, systemic infection, and CD4+ T cell depletion in humanized mice infected with HIV-1. J Exp Med. 2007;204(4):705–14. doi:.https://doi.org/10.1084/jem.20062411
- Denton PW, Nochi T, Lim A, Krisko JF, Martinez-Torres F, Choudhary SK, et al. IL-2 receptor γ-chain molecule is critical for intestinal T-cell reconstitution in humanized mice. Mucosal Immunol. 2012;5(5):555–66.
- Deruaz M, Luster AD. BLT humanized mice as model to study HIV vaginal transmission. J Infect Dis. 2013;208(Suppl 2):S131–6. doi:.https://doi.org/10.1093/infdis/jit318
- Stoddart CA, Maidji E, Galkina SA, Kosikova G, Rivera JM, Moreno ME, et al. Superior human leukocyte reconstitution and susceptibility to vaginal HIV transmission in humanized NOD-scid IL-2Rγ(-/-) (NSG) BLT mice. Virology. 2011;417(1):154–60. doi:.https://doi.org/10.1016/j.virol.2011.05.013
- Ladinsky MS, Kieffer C, Olson G, Deruaz M, Vrbanac V, Tager AM, et al. Electron tomography of HIV-1 infection in gut-associated lymphoid tissue. PLoS Pathog. 2014;10(1):e1003899. doi:.https://doi.org/10.1371/journal.ppat.1003899
- de Marco A, Müller B, Glass B, Riches JD, Kräusslich HG, Briggs JA. Structural analysis of HIV-1 maturation using cryo-electron tomography. PLoS Pathog. 2010;6(11):e1001215. doi:.https://doi.org/10.1371/journal.ppat.1001215
- Olesen R, Swanson MD, Kovarova M, Nochi T, Chateau M, Honeycutt JB, et al. ART influences HIV persistence in the female reproductive tract and cervicovaginal secretions. J Clin Invest. 2016;126(3):892–904. doi:.https://doi.org/10.1172/JCI64212
- Wahl A, Swanson MD, Nochi T, Olesen R, Denton PW, Chateau M, et al. Human breast milk and antiretrovirals dramatically reduce oral HIV-1 transmission in BLT humanized mice. PLoS Pathog. 2012;8(6):e1002732. doi:.https://doi.org/10.1371/journal.ppat.1002732
- Li Q, Tso FY, Kang G, Lu W, Li Y, Fan W, et al. Early Initiation of Antiretroviral Therapy Can Functionally Control Productive HIV-1 Infection in Humanized-BLT Mice. J Acquir Immune Defic Syndr. 2015;69(5):519–27. doi:.https://doi.org/10.1097/QAI.0000000000000687
- Sáez-Cirión A, Bacchus C, Hocqueloux L, Avettand-Fenoel V, Girault I, Lecuroux C, et al.; ANRS VISCONTI Study Group. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study. PLoS Pathog. 2013;9(3):e1003211. doi:.https://doi.org/10.1371/journal.ppat.1003211
- Hur EM, Patel SN, Shimizu S, Rao DS, Gnanapragasam PN, An DS, et al. Inhibitory effect of HIV-specific neutralizing IgA on mucosal transmission of HIV in humanized mice. Blood. 2012;120(23):4571–82. doi:.https://doi.org/10.1182/blood-2012-04-422303
- Balazs AB, Ouyang Y, Hong CM, Chen J, Nguyen SM, Rao DS, et al. Vectored immunoprophylaxis protects humanized mice from mucosal HIV transmission. Nat Med. 2014;20(3):296–300. doi:.https://doi.org/10.1038/nm.3471
- Yuan Z, Kang G, Ma F, Lu W, Fan W, Fennessey CM, et al. Recapitulating Cross-Species Transmission of Simian Immunodeficiency Virus SIVcpz to Humans by Using Humanized BLT Mice. J Virol. 2016;90(17):7728–39. doi:.https://doi.org/10.1128/JVI.00860-16
- Deng K, Pertea M, Rongvaux A, Wang L, Durand CM, Ghiaur G, et al. Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations. Nature. 2015;517(7534):381–5. doi:.https://doi.org/10.1038/nature14053
- Honeycutt JB, Wahl A, Archin N, Choudhary S, Margolis D, Garcia JV. HIV-1 infection, response to treatment and establishment of viral latency in a novel humanized T cell-only mouse (TOM) model. Retrovirology. 2013;10(1):121. doi:.https://doi.org/10.1186/1742-4690-10-121
- Honeycutt JB, Wahl A, Baker C, Spagnuolo RA, Foster J, Zakharova O, et al. Macrophages sustain HIV replication in vivo independently of T cells. J Clin Invest. 2016;126(4):1353–66. doi:.https://doi.org/10.1172/JCI84456