Advertisement

The Application of Humanized Mouse Models for the Study of Human Exclusive Viruses

  • Fatemeh Vahedi
  • Elizabeth C. Giles
  • Ali A. AshkarEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1656)

Abstract

The symbiosis between humans and viruses has allowed human tropic pathogens to evolve intricate means of modulating the human immune response to ensure its survival among the human population. In doing so, these viruses have developed profound mechanisms that mesh closely with our human biology. The establishment of this intimate relationship has created a species-specific barrier to infection, restricting the virus-associated pathologies to humans. This specificity diminishes the utility of traditional animal models. Humanized mice offer a model unique to all other means of study, providing an in vivo platform for the careful examination of human tropic viruses and their interaction with human cells and tissues. These types of animal models have provided a reliable medium for the study of human-virus interactions, a relationship that could otherwise not be investigated without questionable relevance to humans.

Key words

Animal models Disease Models Human Humanized mice Immune system Viruses 

References

  1. 1.
    Worobey M, Bjork A, Wertheim JO (2007) Point, counterpoint: the evolution of pathogenic viruses and their human hosts. Annu Rev Ecol Evol Syst 38(1):515–540. doi: 10.1146/annurev.ecolsys.38.091206.095722 CrossRefGoogle Scholar
  2. 2.
    Haley PJ (2003) Species differences in the structure and function of the immune system. Toxicology 188(1):49–71CrossRefGoogle Scholar
  3. 3.
    Yan EG, Munir KM (2004) Regulatory and ethical principles in research involving children and individuals with developmental disabilities. Ethics Behav 14(1):31–49. doi: 10.1207/s15327019eb1401_3 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Partridge TA (2013) The mdx mouse model as a surrogate for Duchenne muscular dystrophy. FEBS J 280(17):4177–4186. doi: 10.1111/febs.12267 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Wilson GK, Stamataki Z (2012) In vitro systems for the study of hepatitis C virus infection. Int J Hepatol 2012:292591. doi: 10.1155/2012/292591 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Marsden MD, Zack JA (2015) Studies of retroviral infection in humanized mice. Virology 479–480:297–309. doi: 10.1016/j.virol.2015.01.017 CrossRefPubMedGoogle Scholar
  7. 7.
    Vandamme TF (2015) Rodent models for human diseases. Eur J Pharmacol 759:84–89. doi: 10.1016/j.ejphar.2015.03.046 CrossRefPubMedGoogle Scholar
  8. 8.
    Shultz LD, Ishikawa F, Greiner DL (2007) Humanized mice in translational biomedical research. Nat Rev Immunol 7(2):118–130CrossRefGoogle Scholar
  9. 9.
    Akkina R (2013) New generation humanized mice for virus research: comparative aspects and future prospects. Virology 435(1):14–28. doi: 10.1016/j.virol.2012.10.007 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Sibal LR, Samson KJ (2001) Nonhuman primates: a critical role in current disease research. ILAR J 42(2):74–84. doi: 10.1093/ilar.42.2.74 CrossRefPubMedGoogle Scholar
  11. 11.
    Messaoudi I, Estep R, Robinson B et al (2011) Nonhuman primate models of human immunology. Antioxid Redox Signal 14(2):261–273. doi: 10.1089/ars.2010.3241 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Lankau EW, Turner PV, Mullan RJ et al (2014) Use of nonhuman primates in research in North America. J Am Assoc Lab Anim Sci 53(3):278–282PubMedPubMedCentralGoogle Scholar
  13. 13.
    Shultz LD, Brehm MA, Garcia-Martinez JV et al (2012) Humanized mice for immune system investigation: progress, promise and challenges. Nat Rev Immunol 12(11):786–798CrossRefGoogle Scholar
  14. 14.
    Bontrop RE (2001) Non-human primates: essential partners in biomedical research. Immunol Rev 183:5–9CrossRefGoogle Scholar
  15. 15.
    Barreiro LB, Marioni JC, Blekhman R et al (2010) Functional comparison of innate immune signaling pathways in primates. PLoS Genet 6(12):e1001249. doi: 10.1371/journal.pgen.1001249 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Justice MJ, Siracusa LD, Stewart AF (2011) Technical approaches for mouse models of human disease. Dis Model Mech 4(3):305–310. doi: 10.1242/dmm.000901 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Davis PH, Stanley SL (2003) Breaking the species barrier: use of SCID mouse–human chimeras for the study of human infectious diseases. Cell Microbiol 5(12):849–860. doi: 10.1046/j.1462-5822.2003.00321.x CrossRefPubMedGoogle Scholar
  18. 18.
    Billerbeck E, Mommersteeg MC, Shlomai A et al (2016) Humanized mice efficiently engrafted with fetal hepatoblasts and syngeneic immune cells develop human monocytes and NK cells. J Hepatol 65(2):334–343. doi: 10.1016/j.jhep.2016.04.022 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Pearson T, Greiner DL, Shultz LD (2008) Creation of “humanized” mice to study human immunity. Curr Protoc Immunol. Chapter 15:Unit 15.21. doi: 10.1002/0471142735.im1521s81
  20. 20.
    Leung W, Ramirez M, Civin CI (1999) Quantity and quality of engrafting cells in cord blood and autologous mobilized peripheral blood. Biol Blood Marrow Transplant 5(2):69–76CrossRefGoogle Scholar
  21. 21.
    Holyoake TL, Nicolini FE, Eaves CJ (1999) Functional differences between transplantable human hematopoietic stem cells from fetal liver, cord blood, and adult marrow. Exp Hematol 27(9):1418–1427. doi: 10.1016/S0301-472X(99)00078-8 CrossRefPubMedGoogle Scholar
  22. 22.
    McCune J, Kaneshima H, Krowka J et al (1991) The SCID-hu mouse: a small animal model for HIV infection and pathogenesis. Annu Rev Immunol 9:399–429. doi: 10.1146/annurev.iy.09.040191.002151 CrossRefPubMedGoogle Scholar
  23. 23.
    Denton PW, Olesen R, Choudhary SK et al (2012) Generation of HIV latency in humanized BLT mice. J Virol 86(1):630–634. doi: 10.1128/JVI.06120-11 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    McCune JM (1996) Development and applications of the SCID-hu mouse model. Semin Immunol 8(4):187–196. doi: 10.1006/smim.1996.0024 CrossRefPubMedGoogle Scholar
  25. 25.
    Nomura T, Watanabe T, Habu S (2008) Humanized mice. Preface. Curr Top Microbiol Immunol 324:v–viPubMedGoogle Scholar
  26. 26.
    Hioki K, Kuramochi T, Endoh S et al (2001) Lack of B cell leakiness in BALB/cA-nu, scid double mutant mice. Exp Anim 50(1):67–72CrossRefGoogle Scholar
  27. 27.
    Gershwin ME, Merchant B, Gelfand MC et al (1975) The natural history and immunopathology of outbred athymic (nude) mice. Clin Immunol Immunopathol 4(3):324–340CrossRefGoogle Scholar
  28. 28.
    Bosma GC, Custer RP, Bosma MJ (1983) A severe combined immunodeficiency mutation in the mouse. Nature 301(5900):527–530CrossRefGoogle Scholar
  29. 29.
    Bosma MJ, Carroll AM (1991) The SCID mouse mutant: definition, characterization, and potential uses. Ann Rev Immunol 9(1):323–350. doi: 10.1146/annurev.iy.09.040191.001543 CrossRefGoogle Scholar
  30. 30.
    Mombaerts P, Iacomini J, Johnson RS et al (1992) RAG-1-deficient mice have no mature B and T lymphocytes. Cell 68(5):869–877. doi: 10.1016/0092-8674(92)90030-G CrossRefPubMedGoogle Scholar
  31. 31.
    Shinkai Y, Rathbun G, Lam KP et al (1992) RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell 68(5):855–867CrossRefGoogle Scholar
  32. 32.
    Shultz LD, Schweitzer PA, Christianson SW et al (1995) Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice. J Immunol 154(1):180–191PubMedGoogle Scholar
  33. 33.
    Brehm MA, Shultz LD, Luban J et al (2013) Overcoming current limitations in humanized mouse research. J Infect Dis 208(Suppl 2):S125–S130. doi: 10.1093/infdis/jit319 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Halstead SB (2015) Pathogenesis of dengue: dawn of a new era. F1000Res 4. doi: 10.12688/f1000research.7024.1
  35. 35.
    Screaton G, Mongkolsapaya J, Yacoub S et al (2015) New insights into the immunopathology and control of dengue virus infection. Nat Rev Immunol 15(12):745–759. doi: 10.1038/nri3916 CrossRefPubMedGoogle Scholar
  36. 36.
    Zompi S, Harris E (2012) Animal models of dengue virus infection. Virus 4(1):62–82. doi: 10.3390/v4010062 CrossRefGoogle Scholar
  37. 37.
    Whitehead SS, Blaney JE, Durbin AP et al (2007) Prospects for a dengue virus vaccine. Nat Rev Microbiol 5(7):518–528. doi: 10.1038/nrmicro1690 CrossRefPubMedGoogle Scholar
  38. 38.
    Bente DA, Melkus MW, Garcia JV et al (2005) Dengue fever in humanized NOD/SCID mice. J Virol 79(21):13797–13799. doi: 10.1128/JVI.79.21.13797-13799.2005 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Yauch LE, Shresta S (2008) Mouse models of dengue virus infection and disease. Antivir Res 80(2):87–93. doi: 10.1016/j.antiviral.2008.06.010 CrossRefPubMedGoogle Scholar
  40. 40.
    Wu SJ, Hayes CG, Dubois DR et al (1995) Evaluation of the severe combined immunodeficient (SCID) mouse as an animal model for dengue viral infection. Am J Trop Med Hyg 52(5):468–476CrossRefGoogle Scholar
  41. 41.
    Bente DA, Rico-Hesse R (2006) Models of dengue virus infection. Drug Discov Today Dis Models 3(1):97–103. doi: 10.1016/j.ddmod.2006.03.014 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Palucka AK, Gatlin J, Blanck JP et al (2003) Human dendritic cell subsets in NOD/SCID mice engrafted with CD34+ hematopoietic progenitors. Blood 102(9):3302–3310. doi: 10.1182/blood-2003-02-0384 CrossRefPubMedGoogle Scholar
  43. 43.
    Cravens PD, Melkus MW, Padgett-Thomas A et al (2005) Development and activation of human dendritic cells in vivo in a xenograft model of human hematopoiesis. Stem Cells 23(2):264–278. doi: 10.1634/stemcells.2004-0116 CrossRefPubMedGoogle Scholar
  44. 44.
    Kuruvilla JG, Troyer RM, Devi S et al (2007) Dengue virus infection and immune response in humanized RAG2(−/−)gamma(c)(−/−) (RAG-hu) mice. Virology 369(1):143–152. doi: 10.1016/j.virol.2007.06.005 CrossRefPubMedGoogle Scholar
  45. 45.
    Mota J, Rico-Hesse R (2009) Humanized mice show clinical signs of dengue fever according to infecting virus genotype. J Virol 83(17):8638–8645. doi: 10.1128/jvi.00581-09 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Jaiswal S, Pearson T, Friberg H et al (2009) Dengue virus infection and virus-specific HLA-A2 restricted immune responses in humanized NOD-scid IL2rgammanull mice. PLoS One 4(10):e7251. doi: 10.1371/journal.pone.0007251 CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Jaiswal S, Pazoles P, Woda M et al (2012) Enhanced humoral and HLA-A2-restricted dengue virus-specific T-cell responses in humanized BLT NSG mice. Immunology 136(3):334–343. doi: 10.1111/j.1365-2567.2012.03585.x CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Jaiswal S, Smith K, Ramirez A et al (2015) Dengue virus infection induces broadly cross-reactive human IgM antibodies that recognize intact virions in humanized BLT-NSG mice. Exp Biol Med (Maywood) 240(1):67–78. doi: 10.1177/1535370214546273 CrossRefGoogle Scholar
  49. 49.
    Frias-Staheli N, Dorner M, Marukian S et al (2014) Utility of humanized BLT mice for analysis of dengue virus infection and antiviral drug testing. J Virol 88(4):2205–2218. doi: 10.1128/JVI.03085-13 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Cox J, Mota J, Sukupolvi-Petty S et al (2012) Mosquito bite delivery of dengue virus enhances immunogenicity and pathogenesis in humanized mice. J Virol 86(14):7637–7649. doi: 10.1128/jvi.00534-12 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Mota J, Rico-Hesse R (2011) Dengue virus tropism in humanized mice recapitulates human dengue fever. PLoS One 6(6):e20762. doi: 10.1371/journal.pone.0020762 CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Subramanya S, Kim SS, Abraham S et al (2010) Targeted delivery of small interfering RNA to human dendritic cells to suppress dengue virus infection and associated proinflammatory cytokine production. J Virol 84(5):2490–2501. doi: 10.1128/JVI.02105-08 CrossRefPubMedGoogle Scholar
  53. 53.
    Sridharan A, Chen Q, Tang KF et al (2013) Inhibition of megakaryocyte development in the bone marrow underlies dengue virus-induced thrombocytopenia in humanized mice. J Virol 87(21):11648–11658. doi: 10.1128/JVI.01156-13 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Johnson KM, Lange JV, Webb PA et al (1977) Isolation and partial characterisation of a new virus causing acute haemorrhagic fever in Zaire. Lancet 1(8011):569–571CrossRefGoogle Scholar
  55. 55.
    Martinez MJ, Salim AM, Hurtado JC et al (2015) Ebola virus infection: overview and update on prevention and treatment. Infect Dis Ther 4(4):365–390. doi: 10.1007/s40121-015-0079-5 CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Lever RA, Whitty CJ (2016) Ebola virus disease: emergence, outbreak and future directions. Br Med Bull 117(1):95–106. doi: 10.1093/bmb/ldw005 CrossRefPubMedGoogle Scholar
  57. 57.
    Ludtke A, Oestereich L, Ruibal P et al (2015) Ebola virus disease in mice with transplanted human hematopoietic stem cells. J Virol 89(8):4700–4704. doi: 10.1128/JVI.03546-14 CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Bray M (2001) The role of the type I interferon response in the resistance of mice to filovirus infection. J Gen Virol 82(Pt 6):1365–1373. doi: 10.1099/0022-1317-82-6-1365 CrossRefPubMedGoogle Scholar
  59. 59.
    Ebihara H, Takada A, Kobasa D et al (2006) Molecular determinants of Ebola virus virulence in mice. PLoS Pathog 2(7):e73. doi: 10.1371/journal.ppat.0020073 CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Prescott J, Feldmann H (2016) Humanized mice—a neoteric animal disease model for Ebola virus? J Infect Dis 213(5):691–693. doi: 10.1093/infdis/jiv539 CrossRefPubMedGoogle Scholar
  61. 61.
    Bird BH, Spengler JR, Chakrabarti AK et al (2016) Humanized mouse model of Ebola virus disease mimics the immune responses in human disease. J Infect Dis 213(5):703–711. doi: 10.1093/infdis/jiv538 CrossRefPubMedGoogle Scholar
  62. 62.
    Fujiwara S, Matsuda G, Imadome K (2013) Humanized mouse models of epstein-barr virus infection and associated diseases. Pathogens 2(1):153–176. doi: 10.3390/pathogens2010153 CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Fujiwara S, Imadome K, Takei M (2015) Modeling EBV infection and pathogenesis in new-generation humanized mice. Exp Mol Med 47:e135. doi: 10.1038/emm.2014.88 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Munz C (2015) EBV infection of mice with reconstituted human immune system components. Curr Top Microbiol Immunol 391:407–423. doi: 10.1007/978-3-319-22834-1_14 CrossRefPubMedGoogle Scholar
  65. 65.
    Rowe M, Young LS, Crocker J et al (1991) Epstein-Barr virus (EBV)-associated lymphoproliferative disease in the SCID mouse model: implications for the pathogenesis of EBV-positive lymphomas in man. J Exp Med 173(1):147–158CrossRefGoogle Scholar
  66. 66.
    Gujer C, Chatterjee B, Landtwing V et al (2015) Animal models of Epstein Barr virus infection. Curr Opin Virol 13:6–10. doi: 10.1016/j.coviro.2015.03.014 CrossRefPubMedGoogle Scholar
  67. 67.
    Ok CY, Li L, Young KH (2015) EBV-driven B-cell lymphoproliferative disorders: from biology, classification and differential diagnosis to clinical management. Exp Mol Med 47:e132. doi: 10.1038/emm.2014.82 CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Takashima K, Ohashi M, Kitamura Y et al (2008) A new animal model for primary and persistent Epstein-Barr virus infection: human EBV-infected rabbit characteristics determined using sequential imaging and pathological analysis. J Med Virol 80(3):455–466. doi: 10.1002/jmv.21102 CrossRefPubMedGoogle Scholar
  69. 69.
    Kutok JL, Wang F (2006) Spectrum of Epstein-Barr virus-associated diseases. Annu Rev Pathol 1:375–404. doi: 10.1146/annurev.pathol.1.110304.100209 CrossRefPubMedGoogle Scholar
  70. 70.
    Ahmed EH, Baiocchi RA (2016) Murine models of Epstein-Barr virus-associated lymphomagenesis. ILAR J 57(1):55–62. doi: 10.1093/ilar/ilv074 CrossRefPubMedGoogle Scholar
  71. 71.
    Chatterjee B, Leung CS, Munz C (2014) Animal models of Epstein Barr virus infection. J Immunol Methods 410:80–87. doi: 10.1016/j.jim.2014.04.009 CrossRefPubMedGoogle Scholar
  72. 72.
    Lieberman PM (2014) Epstein-Barr Virus Turns 50. Science (New York, NY) 343(6177):1323–1325. doi: 10.1126/science.1252786 CrossRefGoogle Scholar
  73. 73.
    Mosier DE, Gulizia RJ, Baird SM et al (1988) Transfer of a functional human immune system to mice with severe combined immunodeficiency. Nature 335(6187):256–259. doi: 10.1038/335256a0 CrossRefPubMedGoogle Scholar
  74. 74.
    Mosier D, Gulizia R, Baird S et al (1989) B cell lymphomas in SCID mice engrafted with human peripheral blood leukocytes. Blood 74(Suppl 1):52aGoogle Scholar
  75. 75.
    Okano M, Taguchi Y, Nakamine H et al (1990) Characterization of Epstein-Barr virus-induced lymphoproliferation derived from human peripheral blood mononuclear cells transferred to severe combined immunodeficient mice. Am J Pathol 137(3):517–522PubMedPubMedCentralGoogle Scholar
  76. 76.
    McCune JM (1991) SCID mice as immune system models. Curr Opin Immunol 3(2):224–228. doi: 10.1016/0952-7915(91)90055-6 CrossRefPubMedGoogle Scholar
  77. 77.
    Johannessen I, Crawford DH (1999) In vivo models for Epstein-Barr virus (EBV)-associated B cell lymphoproliferative disease (BLPD). Rev Med Virol 9(4):263–277CrossRefGoogle Scholar
  78. 78.
    Picchio GR, Kobayashi R, Kirven M et al (1992) Heterogeneity among Epstein-Barr virus-seropositive donors in the generation of Immunoblastic B-cell lymphomas in SCID mice receiving human peripheral blood leukocyte grafts. Cancer Res 52(9):2468–2477PubMedGoogle Scholar
  79. 79.
    Veronese ML, Veronesi A, D'Andrea E et al (1992) Lymphoproliferative disease in human peripheral blood mononuclear cell-injected SCID mice: I. T lymphocyte requirement for B cell tumor generation. J Exp Med 176(6):1763–1767CrossRefGoogle Scholar
  80. 80.
    Mosier DE (1996) Viral pathogenesis in hu-PBL-SCID mice. Semin Immunol 8(4):255–262. doi: 10.1006/smim.1996.0032 CrossRefPubMedGoogle Scholar
  81. 81.
    Baiocchi RA, Ross ME, Tan JC et al (1995) Lymphomagenesis in the SCID-hu mouse involves abundant production of human interleukin-10. Blood 85(4):1063–1074PubMedGoogle Scholar
  82. 82.
    Islas-Ohlmayer M, Padgett-Thomas A, Domiati-Saad R et al (2004) Experimental infection of NOD/SCID mice reconstituted with human CD34+ cells with Epstein-Barr virus. J Virol 78(24):13891–13900. doi: 10.1128/JVI.78.24.13891-13900.2004 CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Ma SD, Hegde S, Young KH et al (2011) 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 85(1):165–177. doi: 10.1128/JVI.01512-10 CrossRefPubMedGoogle Scholar
  84. 84.
    Wagar EJ, Cromwell MA, Shultz LD et al (2000) Regulation of human cell engraftment and development of EBV-related lymphoproliferative disorders in Hu-PBL-scid mice. J Immunol 165(1):518–527CrossRefGoogle Scholar
  85. 85.
    Yajima M, Imadome K, Nakagawa A et al (2008) 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 198(5):673–682. doi: 10.1086/590502 CrossRefPubMedGoogle Scholar
  86. 86.
    Yajima M, Imadome K, Nakagawa A et al (2009) T cell-mediated control of Epstein-Barr virus infection in humanized mice. J Infect Dis 200(10):1611–1615. doi: 10.1086/644644 CrossRefPubMedGoogle Scholar
  87. 87.
    Kuwana Y, Takei M, Yajima M et al (2011) Epstein-Barr virus induces erosive arthritis in humanized mice. PLoS One 6(10):e26630. doi: 10.1371/journal.pone.0026630 CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Goudarzipour K, Kajiyazdi M, Mahdaviyani A (2013) Epstein-barr virus-induced hemophagocytic lymphohistiocytosis. Int J Hematol Oncol Stem Cell Res 7(1):42–45PubMedPubMedCentralGoogle Scholar
  89. 89.
    Sato K, Misawa N, Nie C et al (2011) A novel animal model of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in humanized mice. Blood 117(21):5663–5673. doi: 10.1182/blood-2010-09-305979 CrossRefPubMedGoogle Scholar
  90. 90.
    Lee EK, Joo EH, Song KA et al (2015) Effects of lymphocyte profile on development of EBV-induced lymphoma subtypes in humanized mice. Proc Natl Acad Sci U S A 112(42):13081–13086. doi: 10.1073/pnas.1407075112 CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Chijioke O, Muller A, Feederle R et al (2013) Human natural killer cells prevent infectious mononucleosis features by targeting lytic Epstein-Barr virus infection. Cell Rep 5(6):1489–1498. doi: 10.1016/j.celrep.2013.11.041 CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    White RE, Ramer PC, Naresh KN et al (2012) EBNA3B-deficient EBV promotes B cell lymphomagenesis in humanized mice and is found in human tumors. J Clin Invest 122(4):1487–1502. doi: 10.1172/JCI58092 CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Wahl A, Linnstaedt SD, Esoda C et al (2013) A cluster of virus-encoded microRNAs accelerates acute systemic Epstein-Barr virus infection but does not significantly enhance virus-induced oncogenesis in vivo. J Virol 87(10):5437–5446. doi: 10.1128/JVI.00281-13 CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Antsiferova O, Muller A, Ramer PC et al (2014) Adoptive transfer of EBV specific CD8+ T cell clones can transiently control EBV infection in humanized mice. PLoS Pathog 10(8):e1004333. doi: 10.1371/journal.ppat.1004333 CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Traggiai E, Chicha L, Mazzucchelli L et al (2004) Development of a human adaptive immune system in cord blood cell-transplanted mice. Science 304(5667):104–107. doi: 10.1126/science.1093933 CrossRefPubMedGoogle Scholar
  96. 96.
    Griffiths P, Baraniak I, Reeves M (2015) The pathogenesis of human cytomegalovirus. J Pathol 235(2):288–297. doi: 10.1002/path.4437 CrossRefPubMedGoogle Scholar
  97. 97.
    Jean Beltran PM, Cristea IM (2014) The life cycle and pathogenesis of human cytomegalovirus infection: lessons from proteomics. Expert Rev Proteomics 11(6):697–711. doi: 10.1586/14789450.2014.971116 CrossRefPubMedGoogle Scholar
  98. 98.
    Crawford LB, Streblow DN, Hakki M et al (2015) Humanized mouse models of human cytomegalovirus infection. Curr Opin Virol 13:86–92. doi: 10.1016/j.coviro.2015.06.006 CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Maidji E, Kosikova G, Joshi P et al (2012) Impaired surfactant production by alveolar epithelial cells in a SCID-hu lung mouse model of congenital human cytomegalovirus infection. J Virol 86(23):12795–12805. doi: 10.1128/JVI.01054-12 CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Prichard MN, Quenelle DC, Bidanset DJ et al (2006) Human cytomegalovirus UL27 is not required for viral replication in human tissue implanted in SCID mice. Virol J 3:18. doi: 10.1186/1743-422X-3-18 CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Mocarski ES, Bonyhadi M, Salimi S et al (1993) Human cytomegalovirus in a SCID-hu mouse: thymic epithelial cells are prominent targets of viral replication. Proc Natl Acad Sci U S A 90(1):104–108CrossRefGoogle Scholar
  102. 102.
    Smith MS, Goldman DC, Bailey AS et al (2010) Granulocyte-colony stimulating factor reactivates human cytomegalovirus in a latently infected humanized mouse model. Cell Host Microbe 8(3):284–291. doi: 10.1016/j.chom.2010.08.001 CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Revello MG, Gerna G (2010) Human cytomegalovirus tropism for endothelial/epithelial cells: scientific background and clinical implications. Rev Med Virol 20(3):136–155. doi: 10.1002/rmv.645 CrossRefPubMedGoogle Scholar
  104. 104.
    Brown JM, Kaneshima H, Mocarski ES (1995) Dramatic interstrain differences in the replication of human cytomegalovirus in SCID-hu mice. J Infect Dis 171(6):1599–1603CrossRefGoogle Scholar
  105. 105.
    Wang W, Taylor SL, Leisenfelder SA et al (2005) Human cytomegalovirus genes in the 15-kilobase region are required for viral replication in implanted human tissues in SCID mice. J Virol 79(4):2115–2123. doi: 10.1128/JVI.79.4.2115-2123.2005 CrossRefPubMedPubMedCentralGoogle Scholar
  106. 106.
    Tabata T, Petitt M, Fang-Hoover J et al (2012) Cytomegalovirus impairs cytotrophoblast-induced lymphangiogenesis and vascular remodeling in an in vivo human placentation model. Am J Pathol 181(5):1540–1559. doi: 10.1016/j.ajpath.2012.08.003 CrossRefPubMedPubMedCentralGoogle Scholar
  107. 107.
    Kawahara T, Lisboa LF, Cader S et al (2013) Human cytomegalovirus infection in humanized liver chimeric mice. Hepatol Res 43(6):679–684. doi: 10.1111/j.1872-034X.2012.01116.x CrossRefPubMedGoogle Scholar
  108. 108.
    Kern ER, Rybak RJ, Hartline CB et al (2001) Predictive efficacy of SCID-hu mouse models for treatment of human cytomegalovirus infections. Antivir Chem Chemother 12(Suppl 1):149–156PubMedGoogle Scholar
  109. 109.
    Kern ER, Hartline CB, Rybak RJ et al (2004) Activities of benzimidazole d- and l-ribonucleosides in animal models of cytomegalovirus infections. Antimicrob Agents Chemother 48(5):1749–1755CrossRefGoogle Scholar
  110. 110.
    Bravo FJ, Cardin RD, Bernstein DI (2007) A model of human cytomegalovirus infection in severe combined immunodeficient mice. Antivir Res 76(2):104–110. doi: 10.1016/j.antiviral.2007.06.008 CrossRefPubMedGoogle Scholar
  111. 111.
    Lischka P, Hewlett G, Wunberg T et al (2010) In vitro and in vivo activities of the novel anticytomegalovirus compound AIC246. Antimicrob Agents Chemother 54(3):1290–1297. doi: 10.1128/AAC.01596-09 CrossRefPubMedPubMedCentralGoogle Scholar
  112. 112.
    Weber O, Bender W, Eckenberg P et al (2001) Inhibition of murine cytomegalovirus and human cytomegalovirus by a novel non-nucleosidic compound in vivo. Antivir Res 49(3):179–189CrossRefGoogle Scholar
  113. 113.
    Hakki M, Goldman DC, Streblow DN et al (2014) HCMV infection of humanized mice after transplantation of G-CSF-mobilized peripheral blood stem cells from HCMV-seropositive donors. Biol Blood Marrow Transplant 20(1):132–135. doi: 10.1016/j.bbmt.2013.10.019 CrossRefPubMedGoogle Scholar
  114. 114.
    Umashankar M, Petrucelli A, Cicchini L et al (2011) A novel human cytomegalovirus locus modulates cell type-specific outcomes of infection. PLoS Pathog 7(12):e1002444. doi: 10.1371/journal.ppat.1002444 CrossRefPubMedPubMedCentralGoogle Scholar
  115. 115.
    Houghton M (2009) Discovery of the hepatitis C virus. Liver Int 29(Suppl 1):82–88. doi: 10.1111/j.1478-3231.2008.01925.x CrossRefPubMedGoogle Scholar
  116. 116.
    Washburn ML, Bility MT, Zhang L et al (2011) A humanized mouse model to study hepatitis C virus infection, immune response, and liver disease. Gastroenterology 140(4):1334–1344. doi: 10.1053/j.gastro.2011.01.001 CrossRefPubMedPubMedCentralGoogle Scholar
  117. 117.
    von Schaewen M, Ploss A (2014) Murine models of hepatitis C: what can we look forward to? Antivir Res 104:15–22. doi: 10.1016/j.antiviral.2014.01.007 CrossRefGoogle Scholar
  118. 118.
    Marra E, Turrini P, Tripodi M et al (2012) Intrablastocyst injection with human CD34+/CD133+ cells increase survival of immunocompetent fumarylacetoacetate hydrolase knockout mice. Lab Anim 46(4):280–286. doi: 10.1258/la.2012.012038 CrossRefPubMedGoogle Scholar
  119. 119.
    Meuleman P, Leroux-Roels G (2008) The human liver-uPA-SCID mouse: a model for the evaluation of antiviral compounds against HBV and HCV. Antivir Res 80(3):231–238. doi: 10.1016/j.antiviral.2008.07.006 CrossRefPubMedGoogle Scholar
  120. 120.
    Mesalam AA, Vercauteren K, Meuleman P (2016) Mouse systems to model hepatitis C virus treatment and associated resistance. Virus 8(6):176. doi: 10.3390/v8060176 CrossRefGoogle Scholar
  121. 121.
    Dandri M, Burda MR, Torok E et al (2001) Repopulation of mouse liver with human hepatocytes and in vivo infection with hepatitis B virus. Hepatology 33(4):981–988. doi: 10.1053/jhep.2001.23314 CrossRefPubMedGoogle Scholar
  122. 122.
    Bissig KD, Wieland SF, Tran P et al (2010) Human liver chimeric mice provide a model for hepatitis B and C virus infection and treatment. J Clin Invest 120(3):924–930. doi: 10.1172/JCI40094 CrossRefPubMedPubMedCentralGoogle Scholar
  123. 123.
    Tesfaye A, Stift J, Maric D et al (2013) Chimeric mouse model for the infection of hepatitis B and C viruses. PLoS One 8(10):e77298. doi: 10.1371/journal.pone.0077298 CrossRefPubMedPubMedCentralGoogle Scholar
  124. 124.
    Kosaka K, Hiraga N, Imamura M et al (2013) A novel TK-NOG based humanized mouse model for the study of HBV and HCV infections. Biochem Biophys Res Commun 441(1):230–235. doi: 10.1016/j.bbrc.2013.10.040 CrossRefPubMedGoogle Scholar
  125. 125.
    Heckel JL, Sandgren EP, Degen JL et al (1990) Neonatal bleeding in transgenic mice expressing urokinase-type plasminogen activator. Cell 62(3):447–456CrossRefGoogle Scholar
  126. 126.
    Rhim JA, Sandgren EP, Degen JL et al (1994) Replacement of diseased mouse liver by hepatic cell transplantation. Science 263(5150):1149–1152CrossRefGoogle Scholar
  127. 127.
    Azuma H, Paulk N, Ranade A et al (2007) Robust expansion of human hepatocytes in fah−/−/Rag2−/−/Il2rg−/− mice. Nat Biotechnol 25(8):903–910. doi: 10.1038/nbt1326 CrossRefPubMedPubMedCentralGoogle Scholar
  128. 128.
    Joyce MA, Walters KA, Lamb SE et al (2009) HCV induces oxidative and ER stress, and sensitizes infected cells to apoptosis in SCID/Alb-uPA mice. PLoS Pathog 5(2):e1000291. doi: 10.1371/journal.ppat.1000291 CrossRefPubMedPubMedCentralGoogle Scholar
  129. 129.
    Fafi-Kremer S, Fofana I, Soulier E et al (2010) Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation. J Exp Med 207(9):2019–2031. doi: 10.1084/jem.20090766 CrossRefPubMedPubMedCentralGoogle Scholar
  130. 130.
    Brown RJ, Hudson N, Wilson G et al (2012) Hepatitis C virus envelope glycoprotein fitness defines virus population composition following transmission to a new host. J Virol 86(22):11956–11966. doi: 10.1128/JVI.01079-12 CrossRefPubMedPubMedCentralGoogle Scholar
  131. 131.
    Singaravelu R, Chen R, Lyn RK et al (2014) Hepatitis C virus induced up-regulation of microRNA-27: a novel mechanism for hepatic steatosis. Hepatology 59(1):98–108. doi: 10.1002/hep.26634 CrossRefPubMedGoogle Scholar
  132. 132.
    Vassilaki N, Friebe P, Meuleman P et al (2008) Role of the hepatitis C virus core+1 open reading frame and core cis-acting RNA elements in viral RNA translation and replication. J Virol 82(23):11503–11515. doi: 10.1128/JVI.01640-08 CrossRefPubMedPubMedCentralGoogle Scholar
  133. 133.
    Gottwein JM, Jensen TB, Mathiesen CK et al (2011) Development and application of hepatitis C reporter viruses with genotype 1 to 7 core-nonstructural protein 2 (NS2) expressing fluorescent proteins or luciferase in modified JFH1 NS5A. J Virol 85(17):8913–8928. doi: 10.1128/JVI.00049-11 CrossRefPubMedPubMedCentralGoogle Scholar
  134. 134.
    Pietschmann T, Zayas M, Meuleman P et al (2009) Production of infectious genotype 1b virus particles in cell culture and impairment by replication enhancing mutations. PLoS Pathog 5(6):e1000475. doi: 10.1371/journal.ppat.1000475 CrossRefPubMedPubMedCentralGoogle Scholar
  135. 135.
    Kaul A, Woerz I, Meuleman P et al (2007) Cell culture adaptation of hepatitis C virus and in vivo viability of an adapted variant. J Virol 81(23):13168–13179. doi: 10.1128/JVI.01362-07 CrossRefPubMedPubMedCentralGoogle Scholar
  136. 136.
    Vanwolleghem T, Bukh J, Meuleman P et al (2008) Polyclonal immunoglobulins from a chronic hepatitis C virus patient protect human liver-chimeric mice from infection with a homologous hepatitis C virus strain. Hepatology 47(6):1846–1855. doi: 10.1002/hep.22244 CrossRefPubMedGoogle Scholar
  137. 137.
    Law M, Maruyama T, Lewis J et al (2008) Broadly neutralizing antibodies protect against hepatitis C virus quasispecies challenge. Nat Med 14(1):25–27. doi: 10.1038/nm1698 CrossRefPubMedGoogle Scholar
  138. 138.
    Meuleman P, Hesselgesser J, Paulson M et al (2008) Anti-CD81 antibodies can prevent a hepatitis C virus infection in vivo. Hepatology 48(6):1761–1768. doi: 10.1002/hep.22547 CrossRefPubMedGoogle Scholar
  139. 139.
    Kneteman NM, Weiner AJ, O'Connell J et al (2006) Anti-HCV therapies in chimeric scid-Alb/uPA mice parallel outcomes in human clinical application. Hepatology 43(6):1346–1353. doi: 10.1002/hep.21209 CrossRefPubMedGoogle Scholar
  140. 140.
    Reiser M, Hinrichsen H, Benhamou Y et al (2005) Antiviral efficacy of NS3-serine protease inhibitor BILN-2061 in patients with chronic genotype 2 and 3 hepatitis C. Hepatology 41(4):832–835. doi: 10.1002/hep.20612 CrossRefPubMedGoogle Scholar
  141. 141.
    Vanwolleghem T, Meuleman P, Libbrecht L et al (2007) Ultra-rapid cardiotoxicity of the hepatitis C virus protease inhibitor BILN 2061 in the Urokinase-type plasminogen activator mouse. Gastroenterology 133(4):1144–1155. doi: 10.1053/j.gastro.2007.07.007 CrossRefPubMedGoogle Scholar
  142. 142.
    Inoue K, Umehara T, Ruegg UT et al (2007) Evaluation of a cyclophilin inhibitor in hepatitis C virus-infected chimeric mice in vivo. Hepatology 45(4):921–928. doi: 10.1002/hep.21587 CrossRefPubMedGoogle Scholar
  143. 143.
    Umehara T, Sudoh M, Yasui F et al (2006) Serine palmitoyltransferase inhibitor suppresses HCV replication in a mouse model. Biochem Biophys Res Commun 346(1):67–73. doi: 10.1016/j.bbrc.2006.05.085 CrossRefPubMedGoogle Scholar
  144. 144.
    Hsu EC, Hsi B, Hirota-Tsuchihara M et al (2003) Modified apoptotic molecule (BID) reduces hepatitis C virus infection in mice with chimeric human livers. Nat Biotechnol 21(5):519–525. doi: 10.1038/nbt817 CrossRefPubMedGoogle Scholar
  145. 145.
    Overturf K, Al-Dhalimy M, Tanguay R et al (1996) Hepatocytes corrected by gene therapy are selected in vivo in a murine model of hereditary tyrosinaemia type I. Nat Genet 12(3):266–273. doi: 10.1038/ng0396-266 CrossRefPubMedGoogle Scholar
  146. 146.
    Shafritz DA (2007) A human hepatocyte factory. Nat Biotechnol 25(8):871–872. doi: 10.1038/nbt0807-871 CrossRefPubMedGoogle Scholar
  147. 147.
    Robinet E, Baumert TF (2011) A first step towards a mouse model for hepatitis C virus infection containing a human immune system. J Hepatol 55(3):718–720. doi: 10.1016/j.jhep.2011.02.038 CrossRefPubMedGoogle Scholar
  148. 148.
    Gutti TL, Knibbe JS, Makarov E et al (2014) Human hepatocytes and hematolymphoid dual reconstitution in treosulfan-conditioned uPA-NOG mice. Am J Pathol 184(1):101–109. doi: 10.1016/j.ajpath.2013.09.008 CrossRefPubMedPubMedCentralGoogle Scholar
  149. 149.
    Strick-Marchand H, Dusseaux M, Darche S et al (2015) A novel mouse model for stable engraftment of a human immune system and human hepatocytes. PLoS One 10(3):e0119820. doi: 10.1371/journal.pone.0119820 CrossRefPubMedPubMedCentralGoogle Scholar
  150. 150.
    Montagnier L (2010) 25 years after HIV discovery: prospects for cure and vaccine. Virology 397(2):248–254. doi: 10.1016/j.virol.2009.10.045 CrossRefPubMedGoogle Scholar
  151. 151.
    Hsiung GD (1987) Perspectives on retroviruses and the etiologic agent of AIDS. Yale J Biol Med 60(6):505–514PubMedPubMedCentralGoogle Scholar
  152. 152.
    Collaborators GH, Wang H, Wolock TM et al (2016) Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2015: the global burden of disease study 2015. Lancet HIV 3(8):e361–e387. doi: 10.1016/S2352-3018(16)30087-X CrossRefGoogle Scholar
  153. 153.
    Owen A, Rannard S (2016) Strengths, weaknesses, opportunities and challenges for long acting injectable therapies: insights for applications in HIV therapy. Adv Drug Deliv Rev 103:144–156. doi: 10.1016/j.addr.2016.02.003 CrossRefPubMedPubMedCentralGoogle Scholar
  154. 154.
    Rahman SM, Vaidya NK, Zou X (2016) Impact of early treatment programs on HIV epidemics: an immunity-based mathematical model. Math Biosci 280:38–49. doi: 10.1016/j.mbs.2016.07.009 CrossRefPubMedGoogle Scholar
  155. 155.
    Wainberg MA, Zaharatos GJ, Brenner BG (2011) Development of antiretroviral drug resistance. N Engl J Med 365(7):637–646. doi: 10.1056/NEJMra1004180 CrossRefPubMedGoogle Scholar
  156. 156.
    Okoye AA, Picker LJ (2013) CD4(+) T-cell depletion in HIV infection: mechanisms of immunological failure. Immunol Rev 254(1):54–64. doi: 10.1111/imr.12066 CrossRefPubMedPubMedCentralGoogle Scholar
  157. 157.
    Denton PW, Garcia JV (2011) Humanized mouse models of HIV infection. AIDS Rev 13(3):135–148PubMedPubMedCentralGoogle Scholar
  158. 158.
    Koka PS, Fraser JK, Bryson Y et al (1998) Human immunodeficiency virus inhibits multilineage hematopoiesis in vivo. J Virol 72(6):5121–5127PubMedPubMedCentralGoogle Scholar
  159. 159.
    Mosier DE, Gulizia RJ, MacIsaac PD et al (1993) Resistance to human immunodeficiency virus 1 infection of SCID mice reconstituted with peripheral blood leukocytes from donors vaccinated with vaccinia gp160 and recombinant gp160. Proc Natl Acad Sci U S A 90(6):2443–2447CrossRefGoogle Scholar
  160. 160.
    Gauduin MC, Parren PW, Weir R et al (1997) Passive immunization with a human monoclonal antibody protects hu-PBL-SCID mice against challenge by primary isolates of HIV-1. Nat Med 3(12):1389–1393CrossRefGoogle Scholar
  161. 161.
    Parren PW, Ditzel HJ, Gulizia RJ et al (1995) Protection against HIV-1 infection in hu-PBL-SCID mice by passive immunization with a neutralizing human monoclonal antibody against the gp120 CD4-binding site. AIDS 9(6):F1–F6CrossRefGoogle Scholar
  162. 162.
    van Kuyk R, Torbett BE, Gulizia RJ et al (1994) Cloned human CD8+ cytotoxic T lymphocytes protect human peripheral blood leukocyte-severe combined immunodeficient mice from HIV-1 infection by an HLA-unrestricted mechanism. J Immunol 153(10):4826–4833PubMedGoogle Scholar
  163. 163.
    Denton PW, Garcia JV (2009) Novel humanized murine models for HIV research. Curr HIV/AIDS Rep 6(1):13–19CrossRefGoogle Scholar
  164. 164.
    Bonyhadi ML, Rabin L, Salimi S et al (1993) HIV induces thymus depletion in vivo. Nature 363(6431):728–732. doi: 10.1038/363728a0 CrossRefPubMedGoogle Scholar
  165. 165.
    Stoddart CA, Bales CA, Bare JC et al (2007) Validation of the SCID-hu thy/liv mouse model with four classes of licensed antiretrovirals. PLoS One 2(7):e655. doi: 10.1371/journal.pone.0000655 CrossRefPubMedPubMedCentralGoogle Scholar
  166. 166.
    Policicchio BB, Pandrea I, Apetrei C (2016) Animal models for HIV cure research. Front Immunol 7:12. doi: 10.3389/fimmu.2016.00012 CrossRefPubMedPubMedCentralGoogle Scholar
  167. 167.
    Brooks DG, Kitchen SG, Kitchen CM et al (2001) Generation of HIV latency during thymopoiesis. Nat Med 7(4):459–464. doi: 10.1038/86531 CrossRefPubMedGoogle Scholar
  168. 168.
    Brooks DG, Hamer DH, Arlen PA et al (2003) Molecular characterization, reactivation, and depletion of latent HIV. Immunity 19(3):413–423CrossRefGoogle Scholar
  169. 169.
    Korin YD, Brooks DG, Brown S et al (2002) Effects of prostratin on T-cell activation and human immunodeficiency virus latency. J Virol 76(16):8118–8123CrossRefGoogle Scholar
  170. 170.
    Berges BK, Rowan MR (2011) The utility of the new generation of humanized mice to study HIV-1 infection: transmission, prevention, pathogenesis, and treatment. Retrovirology 8:65. doi: 10.1186/1742-4690-8-65 CrossRefPubMedPubMedCentralGoogle Scholar
  171. 171.
    Hofer U, Baenziger S, Heikenwalder M et al (2008) 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 82(24):12145–12153. doi: 10.1128/JVI.01105-08 CrossRefPubMedPubMedCentralGoogle Scholar
  172. 172.
    Akkina R, Berges BK, Palmer BE et al (2011) Humanized Rag1−/− gammac−/− mice support multilineage hematopoiesis and are susceptible to HIV-1 infection via systemic and vaginal routes. PLoS One 6(6):e20169. doi: 10.1371/journal.pone.0020169 CrossRefPubMedPubMedCentralGoogle Scholar
  173. 173.
    Choudhary SK, Archin NM, Cheema M et al (2012) Latent HIV-1 infection of resting CD4(+) T cells in the humanized Rag2(−)/(−) gammac(−)/(−) mouse. J Virol 86(1):114–120. doi: 10.1128/JVI.05590-11 CrossRefPubMedPubMedCentralGoogle Scholar
  174. 174.
    Holt N, Wang J, Kim K et al (2010) Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo. Nat Biotechnol 28(8):839–847. doi: 10.1038/nbt.1663 CrossRefPubMedPubMedCentralGoogle Scholar
  175. 175.
    Halper-Stromberg A, Lu CL, Klein F et al (2014) Broadly neutralizing antibodies and viral inducers decrease rebound from HIV-1 latent reservoirs in humanized mice. Cell 158(5):989–999. doi: 10.1016/j.cell.2014.07.043 CrossRefPubMedPubMedCentralGoogle Scholar
  176. 176.
    Kirchhoff F (2008) Silencing HIV-1 in vivo. Cell 134(4):566–568. doi: 10.1016/j.cell.2008.08.004 CrossRefPubMedGoogle Scholar
  177. 177.
    Kumar P, Ban HS, Kim SS et al (2008) T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice. Cell 134(4):577–586. doi: 10.1016/j.cell.2008.06.034 CrossRefPubMedPubMedCentralGoogle Scholar
  178. 178.
    Sun Z, Denton PW, Estes JD et al (2007) Intrarectal transmission, systemic infection, and CD4+ T cell depletion in humanized mice infected with HIV-1. J Exp Med 204(4):705–714. doi: 10.1084/jem.20062411 CrossRefPubMedPubMedCentralGoogle Scholar
  179. 179.
    Olesen R, Wahl A, Denton PW et al (2011) Immune reconstitution of the female reproductive tract of humanized BLT mice and their susceptibility to human immunodeficiency virus infection. J Reprod Immunol 88(2):195–203. doi: 10.1016/j.jri.2010.11.005 CrossRefPubMedPubMedCentralGoogle Scholar
  180. 180.
    Watkins RL, Foster JL, Garcia JV (2015) In vivo analysis of Nef's role in HIV-1 replication, systemic T cell activation and CD4(+) T cell loss. Retrovirology 12:61. doi: 10.1186/s12977-015-0187-z CrossRefPubMedPubMedCentralGoogle Scholar
  181. 181.
    Denton PW, Long JM, Wietgrefe SW et al (2014) Targeted cytotoxic therapy kills persisting HIV infected cells during ART. PLoS Pathog 10(1):e1003872. doi: 10.1371/journal.ppat.1003872 CrossRefPubMedPubMedCentralGoogle Scholar
  182. 182.
    Shimizu S, Ringpis GE, Marsden MD et al (2015) RNAi-mediated CCR5 knockdown provides HIV-1 resistance to memory T cells in humanized BLT mice. Mol Ther Nucleic Acids e227:4. doi: 10.1038/mtna.2015.3 CrossRefGoogle Scholar
  183. 183.
    Martin JL, Maldonado JO, Mueller JD et al (2016) Molecular studies of HTLV-1 replication: an update. Virus 8(2). doi: 10.3390/v8020031 CrossRefGoogle Scholar
  184. 184.
    Goncalves DU, Proietti FA, Ribas JG et al (2010) Epidemiology, treatment, and prevention of human T-cell leukemia virus type 1-associated diseases. Clin Microbiol Rev 23(3):577–589. doi: 10.1128/CMR.00063-09 CrossRefPubMedPubMedCentralGoogle Scholar
  185. 185.
    Manel N, Battini JL, Taylor N et al (2005) HTLV-1 tropism and envelope receptor. Oncogene 24(39):6016–6025. doi: 10.1038/sj.onc.1208972 CrossRefPubMedGoogle Scholar
  186. 186.
    Azran I, Schavinsky-Khrapunsky Y, Aboud M (2004) Role of tax protein in human T-cell leukemia virus type-I leukemogenicity. Retrovirology 1:20. doi: 10.1186/1742-4690-1-20 CrossRefPubMedPubMedCentralGoogle Scholar
  187. 187.
    Tezuka K, Xun R, Tei M et al (2014) An animal model of adult T-cell leukemia: humanized mice with HTLV-1-specific immunity. Blood 123(3):346–355. doi: 10.1182/blood-2013-06-508861 CrossRefPubMedGoogle Scholar
  188. 188.
    Feuer G, Zack JA, Harrington WJ Jr et al (1993) Establishment of human T-cell leukemia virus type I T-cell lymphomas in severe combined immunodeficient mice. Blood 82(3):722–731PubMedGoogle Scholar
  189. 189.
    Kondo A, Imada K, Hattori T et al (1993) A model of in vivo cell proliferation of adult T-cell leukemia. Blood 82(8):2501–2509PubMedGoogle Scholar
  190. 190.
    Van Duyne R, Pedati C, Guendel I et al (2009) The utilization of humanized mouse models for the study of human retroviral infections. Retrovirology 6:76. doi: 10.1186/1742-4690-6-76 CrossRefPubMedPubMedCentralGoogle Scholar
  191. 191.
    Miyazato P, Yasunaga J, Taniguchi Y et al (2006) De novo human T-cell leukemia virus type 1 infection of human lymphocytes in NOD-SCID, common gamma-chain knockout mice. J Virol 80(21):10683–10691. doi: 10.1128/JVI.01009-06 CrossRefPubMedPubMedCentralGoogle Scholar
  192. 192.
    Takajo I, Umeki K, Morishita K et al (2007) Engraftment of peripheral blood mononuclear cells from human T-lymphotropic virus type 1 carriers in NOD/SCID/gammac(null) (NOG) mice. Int J Cancer 121(10):2205–2211. doi: 10.1002/ijc.22972 CrossRefPubMedGoogle Scholar
  193. 193.
    Panfil AR, Al-Saleem JJ, Green PL (2013) Animal models utilized in HTLV-1 research. Virology (Auckl) 4:49–59. doi: 10.4137/VRT.S12140 CrossRefGoogle Scholar
  194. 194.
    Villaudy J, Wencker M, Gadot N et al (2011) HTLV-1 propels thymic human T cell development in “human immune system” Rag2(−)/(−) gamma c(−)/(−) mice. PLoS Pathog 7(9):e1002231. doi: 10.1371/journal.ppat.1002231 CrossRefPubMedPubMedCentralGoogle Scholar
  195. 195.
    Martin F, Bangham CR, Ciminale V et al (2011) Conference highlights of the 15th international conference on human retrovirology: HTLV and related retroviruses, 4-8 June 2011, Leuven, Gembloux, Belgium. Retrovirology 8:86. doi: 10.1186/1742-4690-8-86 CrossRefPubMedPubMedCentralGoogle Scholar
  196. 196.
    Tezuka K, Xun R, Tei M et al (2011) Inverse correlation between tax and CD25 expressions in HTLV-1 infected CD4 T-cells in vivo. Retrovirology 8(1):1–1. doi: 10.1186/1742-4690-8-s1-a14 CrossRefGoogle Scholar
  197. 197.
    Peres E, Bagdassarian E, This S et al (2015) From immunodeficiency to humanization: the contribution of mouse models to explore HTLV-1 Leukemogenesis. Virus 7(12):6371–6386. doi: 10.3390/v7122944 CrossRefGoogle Scholar
  198. 198.
    Feuer G, Fraser JK, Zack JA et al (1996) Human T-cell leukemia virus infection of human hematopoietic progenitor cells: maintenance of virus infection during differentiation in vitro and in vivo. J Virol 70(6):4038–4044PubMedPubMedCentralGoogle Scholar
  199. 199.
    Saito M, Tanaka R, Fujii H et al (2014) The neutralizing function of the anti-HTLV-1 antibody is essential in preventing in vivo transmission of HTLV-1 to human T cells in NOD-SCID/gammacnull (NOG) mice. Retrovirology 11:74. doi: 10.1186/s12977-014-0074-z CrossRefPubMedPubMedCentralGoogle Scholar
  200. 200.
    Hiyoshi M, Okuma K, Tateyama S et al (2015) Furin-dependent CCL17-fused recombinant toxin controls HTLV-1 infection by targeting and eliminating infected CCR4-expressing cells in vitro and in vivo. Retrovirology 12:73. doi: 10.1186/s12977-015-0199-8 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  • Fatemeh Vahedi
    • 1
    • 2
  • Elizabeth C. Giles
    • 1
    • 2
  • Ali A. Ashkar
    • 1
    • 2
    Email author
  1. 1.Department of Pathology and Molecular MedicineMcMaster Immunology Research CentreHamiltonCanada
  2. 2.MG DeGroote Institute for Infectious Disease ResearchMcMaster Immunology Research CentreHamiltonCanada

Personalised recommendations