1887

Abstract

The human herpesviruses (HHVs) are remarkably successful human pathogens, with some members of the family successfully establishing infection in the vast majority of humans worldwide. Although many HHV infections result in asymptomatic infection or mild disease, there are rare cases of severe disease and death found with nearly every HHV. Many of the pathogenic mechanisms of these viruses are poorly understood, and in many cases, effective antiviral drugs are lacking. Only a single vaccine exists for the HHVs and researchers have been unable to develop treatments to cure the persistent infections associated with HHVs. A major hindrance to HHV research has been the lack of suitable animal models, with the notable exception of the herpes simplex viruses. One promising area for HHV research is the use of humanized mouse models, in which human cells or tissues are transplanted into immunodeficient mice. Current humanized mouse models mostly transplant human haematopoietic stem cells (HSCs), resulting in the production of a variety of human immune cells. Although all HHVs are thought to infect human immune cells, the beta- and gammaherpesviruses extensively infect and establish latency in these cells. Thus, mice humanized with HSCs hold great promise to study these herpesviruses. In this review, we provide a historical perspective on the use of both older and newer humanized mouse models to study HHV infections. The focus is on current developments in using humanized mice to study mechanisms of HHV-induced pathogenesis, human immune responses to HHVs and effectiveness of antiviral drugs.

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2014-10-01
2024-04-26
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References

  1. Abele-Ohl S., Leis M., Wollin M., Mahmoudian S., Hoffmann J., Müller R., Heim C., Spriewald B. M., Weyand M.other authors 2012; Human cytomegalovirus infection leads to elevated levels of transplant arteriosclerosis in a humanized mouse aortic xenograft model. Am J Transplant 12:1720–1729 [View Article][PubMed]
    [Google Scholar]
  2. Adams M. J., Carstens E. B. 2012; Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses (2012). Arch Virol 157:1411–1422 [View Article][PubMed]
    [Google Scholar]
  3. Appleton A. L., Sviland L., Peiris J. S., Taylor C. E., Wilkes J., Green M. A., Pearson A. D., Kelly P. J., Malcolm A. J.other authors 1995; Human herpes virus-6 infection in marrow graft recipients: role in pathogenesis of graft-versus-host disease. Newcastle upon Tyne Bone Marrow Transport Group. Bone Marrow Transplant 16:777–782[PubMed]
    [Google Scholar]
  4. Azuma H., Paulk N., Ranade A., Dorrell C., Al-Dhalimy M., Ellis E., Strom S., Kay M. A., Finegold M., Grompe M. 2007; Robust expansion of human hepatocytes in Fah–/–/Rag2–/–/Il2rg–/– mice. Nat Biotechnol 25:903–910 [View Article][PubMed]
    [Google Scholar]
  5. Bidanset D. J., Rybak R. J., Hartline C. B., Kern E. R. 2001; Replication of human cytomegalovirus in severe combined immunodeficient mice implanted with human retinal tissue. J Infect Dis 184:192–195 [View Article][PubMed]
    [Google Scholar]
  6. Boshoff C., Gao S. J., Healy L. E., Matthews S., Thomas A. J., Coignet L., Warnke R. A., Strauchen J. A., Matutes E.other authors 1998; Establishing a KSHV+ cell line (BCP-1) from peripheral blood and characterizing its growth in Nod/SCID mice. Blood 91:1671–1679[PubMed]
    [Google Scholar]
  7. Bravo F. J., Cardin R. D., Bernstein D. I. 2007; A model of human cytomegalovirus infection in severe combined immunodeficient mice. Antiviral Res 76:104–110 [View Article][PubMed]
    [Google Scholar]
  8. Carbone A., Cesarman E., Spina M., Gloghini A., Schulz T. F. 2009; HIV-associated lymphomas and gamma-herpesviruses. Blood 113:1213–1224 [View Article][PubMed]
    [Google Scholar]
  9. Chen Q., Khoury M., Chen J. 2009; Expression of human cytokines dramatically improves reconstitution of specific human-blood lineage cells in humanized mice. Proc Natl Acad Sci U S A 106:21783–21788 [View Article][PubMed]
    [Google Scholar]
  10. Cocco M., Bellan C., Tussiwand R., Corti D., Traggiai E., Lazzi S., Mannucci S., Bronz L., Palummo N.other authors 2008; CD34+ cord blood cell-transplanted Rag2–/– γc–/– mice as a model for Epstein–Barr virus infection. Am J Pathol 173:1369–1378 [View Article][PubMed]
    [Google Scholar]
  11. D’Agostino G., Aricò E., Santodonato L., Venditti M., Sestili P., Masuelli L., Coletti A., Modesti A., Picchio G.other authors 1999; Type I consensus IFN (IFN-con1) gene transfer into KSHV/HHV-8-infected BCBL-1 cells causes inhibition of viral lytic cycle activation via induction of apoptosis and abrogates tumorigenicity in sCID mice. J Interferon Cytokine Res 19:1305–1316 [View Article][PubMed]
    [Google Scholar]
  12. da Silva S. R., de Oliveira D. E. 2011; HIV, EBV and KSHV: viral cooperation in the pathogenesis of human malignancies. Cancer Lett 305:175–185 [View Article][PubMed]
    [Google Scholar]
  13. Dagna L., Pritchett J. C., Lusso P. 2013; Immunomodulation and immunosuppression by human herpesvirus 6A and 6B. Future Virol 8:273–287 [View Article][PubMed]
    [Google Scholar]
  14. Dash P. K., Gorantla S., Gendelman H. E., Knibbe J., Casale G. P., Makarov E., Epstein A. A., Gelbard H. A., Boska M. D., Poluektova L. Y. 2011; Loss of neuronal integrity during progressive HIV-1 infection of humanized mice. J Neurosci 31:3148–3157 [View Article][PubMed]
    [Google Scholar]
  15. Dittmer D., Stoddart C., Renne R., Linquist-Stepps V., Moreno M. E., Bare C., McCune J. M., Ganem D. 1999; Experimental transmission of Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV-8) to SCID-hu Thy/Liv mice. J Exp Med 190:1857–1868 [View Article][PubMed]
    [Google Scholar]
  16. Emery V. C., Atkins M. C., Bowen E. F., Clark D. A., Johnson M. A., Kidd I. M., McLaughlin J. E., Phillips A. N., Strappe P. M., Griffiths P. D. 1999; Interactions between beta-herpesviruses and human immunodeficiency virus in vivo: evidence for increased human immunodeficiency viral load in the presence of human herpesvirus 6. J Med Virol 57:278–282 [View Article][PubMed]
    [Google Scholar]
  17. Epstein L. G., Cvetkovich T. A., Lazar E. S., DiLoreto D., Saito Y., James H., del Cerro C., Kaneshima H., McCune J. M.other authors 1994; Human neural xenografts: progress in developing an in-vivo model to study human immunodeficiency virus (HIV) and human cytomegalovirus (HCMV) infection. Adv Neuroimmunol 4:257–260 [View Article][PubMed]
    [Google Scholar]
  18. Feederle R., Haar J., Bernhardt K., Linnstaedt S. D., Bannert H., Lips H., Cullen B. R., Delecluse H. J. 2011; The members of an Epstein–Barr virus microRNA cluster cooperate to transform B lymphocytes. J Virol 85:9801–9810 [View Article][PubMed]
    [Google Scholar]
  19. Foreman K. E., Friborg J., Chandran B., Katano H., Sata T., Mercader M., Nabel G. J., Nickoloff B. J. 2001; Injection of human herpesvirus-8 in human skin engrafted on SCID mice induces Kaposi’s sarcoma-like lesions. J Dermatol Sci 26:182–193 [View Article][PubMed]
    [Google Scholar]
  20. Fuzzati-Armentero M. T., Duchosal M. A. 1998; hu-PBL-SCID mice: an in vivo model of Epstein–Barr virus-dependent lymphoproliferative disease. Histol Histopathol 13:155–168[PubMed]
    [Google Scholar]
  21. Gobbi A., Stoddart C. A., Malnati M. S., Locatelli G., Santoro F., Abbey N. W., Bare C., Linquist-Stepps V., Moreno M. B.other authors 1999; Human herpesvirus 6 (HHV-6) causes severe thymocyte depletion in SCID-hu Thy/Liv mice. J Exp Med 189:1953–1960 [View Article][PubMed]
    [Google Scholar]
  22. Gorantla S., Makarov E., Finke-Dwyer J., Castanedo A., Holguin A., Gebhart C. L., Gendelman H. E., Poluektova L. 2010; Links between progressive HIV-1 infection of humanized mice and viral neuropathogenesis. Am J Pathol 177:2938–2949 [View Article][PubMed]
    [Google Scholar]
  23. Hakki M., Goldman D. C., Streblow D. N., Hamlin K. L., Krekylwich C. N., Fleming W. H., Nelson J. A. 2014; HCMV infection of humanized mice after transplantation of G-CSF-mobilized peripheral blood stem cells from HCMV-seropositive donors. Biol Blood Marrow Transplant 20:132–135 [View Article][PubMed]
    [Google Scholar]
  24. Heuts F., Rottenberg M. E., Salamon D., Rasul E., Adori M., Klein G., Klein E., Nagy N. 2014; T cells modulate Epstein–Barr virus latency phenotypes during infection of humanized mice. J Virol 88:3235–3245 [View Article][PubMed]
    [Google Scholar]
  25. Hu Z., Yang Y. G. 2012; Full reconstitution of human platelets in humanized mice after macrophage depletion. Blood 120:1713–1716 [View Article][PubMed]
    [Google Scholar]
  26. Hu Z., Van Rooijen N., Yang Y. G. 2011; Macrophages prevent human red blood cell reconstitution in immunodeficient mice. Blood 118:5938–5946 [View Article][PubMed]
    [Google Scholar]
  27. Huntington N. D., Legrand N., Alves N. L., Jaron B., Weijer K., Plet A., Corcuff E., Mortier E., Jacques Y.other authors 2009; IL-15 trans-presentation promotes human NK cell development and differentiation in vivo. J Exp Med 206:25–34 [View Article][PubMed]
    [Google Scholar]
  28. Imadome K., Yajima M., Arai A., Nakazawa A., Kawano F., Ichikawa S., Shimizu N., Yamamoto N., Morio T.other authors 2011; Novel mouse xenograft models reveal a critical role of CD4+ T cells in the proliferation of EBV-infected T and NK cells. PLoS Pathog 7:e1002326 [View Article][PubMed]
    [Google Scholar]
  29. Islas-Ohlmayer M., Padgett-Thomas A., Domiati-Saad R., Melkus M. W., Cravens P. D., Martin M. P., Netto G., Garcia J. V. 2004; Experimental infection of NOD/SCID mice reconstituted with human CD34+ cells with Epstein–Barr virus. J Virol 78:13891–13900 [View Article][PubMed]
    [Google Scholar]
  30. Kawahara T., Lisboa L. F., Cader S., Douglas D. N., Nourbakhsh M., Pu C. H., Lewis J. T., Churchill T. A., Humar A., Kneteman N. M. 2013; Human cytomegalovirus infection in humanized liver chimeric mice. Hepatol Res 43:679–684 [View Article][PubMed]
    [Google Scholar]
  31. Kern E. R. 2006; Pivotal role of animal models in the development of new therapies for cytomegalovirus infections. Antiviral Res 71:164–171 [View Article][PubMed]
    [Google Scholar]
  32. Ku C. C., Zerboni L., Ito H., Graham B. S., Wallace M., Arvin A. M. 2004; Varicella-zoster virus transfer to skin by T cells and modulation of viral replication by epidermal cell interferon-alpha. J Exp Med 200:917–925 [View Article][PubMed]
    [Google Scholar]
  33. Kuwana Y., Takei M., Yajima M., Imadome K., Inomata H., Shiozaki M., Ikumi N., Nozaki T., Shiraiwa H.other authors 2011; Epstein–Barr virus induces erosive arthritis in humanized mice. PLoS ONE 6:e26630 [View Article][PubMed]
    [Google Scholar]
  34. Kwant-Mitchell A., Ashkar A. A., Rosenthal K. L. 2009; Mucosal innate and adaptive immune responses against herpes simplex virus type 2 in a humanized mouse model. J Virol 83:10664–10676 [View Article][PubMed]
    [Google Scholar]
  35. Lan K., Murakami M., Bajaj B., Kaul R., He Z., Gan R., Feldman M., Robertson E. S. 2009; Inhibition of KSHV-infected primary effusion lymphomas in NOD/SCID mice by gamma-secretase inhibitor. Cancer Biol Ther 8:2136–2143 [View Article][PubMed]
    [Google Scholar]
  36. Lebbé C., Francès C. 2009; Human herpesvirus 8. Cancer Treat Res 146:169–188 [View Article][PubMed]
    [Google Scholar]
  37. Longnecker R. M., Kieff E., Cohen J. I. 2013; Epstein–Barr virus. In Fields Virology, 6th edn. pp. 1898–1959 Edited by Knipe D. M., Howley P. M. Philadelphia, PA: Lippincott Williams & Wilkins;
    [Google Scholar]
  38. Lusso P., Gallo R. C. 1995; Human herpesvirus 6 in AIDS. Immunol Today 16:67–71 [View Article][PubMed]
    [Google Scholar]
  39. Ma S. D., Hegde S., Young K. H., Sullivan R., Rajesh D., Zhou Y., Jankowska-Gan E., Burlingham W. J., Sun X.other authors 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 85:165–177 [View Article][PubMed]
    [Google Scholar]
  40. Ma S. D., Yu X., Mertz J. E., Gumperz J. E., Reinheim E., Zhou Y., Tang W., Burlingham W. J., Gulley M. L., Kenney S. C. 2012; An Epstein–Barr virus (EBV) mutant with enhanced BZLF1 expression causes lymphomas with abortive lytic EBV infection in a humanized mouse model. J Virol 86:7976–7987 [View Article][PubMed]
    [Google Scholar]
  41. Macchiarini F., Manz M. G., Palucka A. K., Shultz L. D. 2005; Humanized mice: are we there yet?. J Exp Med 202:1307–1311 [View Article][PubMed]
    [Google Scholar]
  42. McCune J. M., Namikawa R., Kaneshima H., Shultz L. D., Lieberman M., Weissman I. L. 1988; The SCID-hu mouse: murine model for the analysis of human hematolymphoid differentiation and function. Science 241:1632–1639 [View Article][PubMed]
    [Google Scholar]
  43. McGeoch D. J., Rixon F. J., Davison A. J. 2006; Topics in herpesvirus genomics and evolution. Virus Res 117:90–104 [View Article][PubMed]
    [Google Scholar]
  44. McGregor A. 2010; Current and new cytomegalovirus antivirals and novel animal model strategies. Inflamm Allergy Drug Targets 9:286–299 [View Article][PubMed]
    [Google Scholar]
  45. Melkus M. W., Estes J. D., Padgett-Thomas A., Gatlin J., Denton P. W., Othieno F. A., Wege A. K., Haase A. T., Garcia J. V. 2006; Humanized mice mount specific adaptive and innate immune responses to EBV and TSST-1. Nat Med 12:1316–1322 [View Article][PubMed]
    [Google Scholar]
  46. Mocarski E. S., Bonyhadi M., Salimi S., McCune J. M., Kaneshima H. 1993; Human cytomegalovirus in a SCID-hu mouse: thymic epithelial cells are prominent targets of viral replication. Proc Natl Acad Sci U S A 90:104–108 [View Article][PubMed]
    [Google Scholar]
  47. Mocarski E. S., Shenk T., Pass R. F. 2007; Cytomegaloviruses. In Fields Virology, 5th edn. pp. 2701–2772 Edited by Knipe D. M., Howley P. M. Philadelphia, PA: Lippincott Williams & Wilkins;
    [Google Scholar]
  48. Moffat J. F., Zerboni L., Kinchington P. R., Grose C., Kaneshima H., Arvin A. M. 1998a; Attenuation of the vaccine Oka strain of varicella-zoster virus and role of glycoprotein C in alphaherpesvirus virulence demonstrated in the SCID-hu mouse. J Virol 72:965–974[PubMed]
    [Google Scholar]
  49. Moffat J. F., Zerboni L., Sommer M. H., Heineman T. C., Cohen J. I., Kaneshima H., Arvin A. M. 1998b; The ORF47 and ORF66 putative protein kinases of varicella-zoster virus determine tropism for human T cells and skin in the SCID-hu mouse. Proc Natl Acad Sci U S A 95:11969–11974 [View Article][PubMed]
    [Google Scholar]
  50. Mosier D. E. 1996; Human immunodeficiency virus infection of human cells transplanted to severe combined immunodeficient mice. Adv Immunol 63:79–125 [View Article][PubMed]
    [Google Scholar]
  51. Mosier D. E., Gulizia R. J., Baird S. M., Wilson D. B. 1988; Transfer of a functional human immune system to mice with severe combined immunodeficiency. Nature 335:256–259 [View Article][PubMed]
    [Google Scholar]
  52. Mosier D. E., Gulizia R. J., Baird S. M., Spector S., Spector D., Kipps T. J., Fox R. I., Carson D. A., Cooper N.other authors 1989; Studies of HIV infection and the development of Epstein–Barr virus-related B cell lymphomas following transfer of human lymphocytes to mice with severe combined immunodeficiency. Curr Top Microbiol Immunol 152:195–199[PubMed]
    [Google Scholar]
  53. Nash A. A., Dutia B. M., Stewart J. P., Davison A. J. 2001; Natural history of murine γ-herpesvirus infection. Philos Trans R Soc Lond B Biol Sci 356:569–579 [View Article][PubMed]
    [Google Scholar]
  54. Orzechowska B. U., Powers M. F., Sprague J., Li H., Yen B., Searles R. P., Axthelm M. K., Wong S. W. 2008; Rhesus macaque rhadinovirus-associated non-Hodgkin lymphoma: animal model for KSHV-associated malignancies. Blood 112:4227–4234 [View Article][PubMed]
    [Google Scholar]
  55. Parsons C. H., Adang L. A., Overdevest J., O’Connor C. M., Taylor J. R. J. Jr, Camerini D., Kedes D. H. 2006; KSHV targets multiple leukocyte lineages during long-term productive infection in NOD/SCID mice. J Clin Invest 116:1963–1973 [View Article][PubMed]
    [Google Scholar]
  56. Pek E. A., Chan T., Reid S., Ashkar A. A. 2011; Characterization and IL-15 dependence of NK cells in humanized mice. Immunobiology 216:218–224 [View Article][PubMed]
    [Google Scholar]
  57. Picchio G. R., Sabbe R. E., Gulizia R. J., McGrath M., Herndier B. G., Mosier D. E. 1997; The KSHV/HHV8-infected BCBL-1 lymphoma line causes tumors in SCID mice but fails to transmit virus to a human peripheral blood mononuclear cell graft. Virology 238:22–29 [View Article][PubMed]
    [Google Scholar]
  58. Prichard M. N., Quenelle D. C., Bidanset D. J., Komazin G., Chou S., Drach J. C., Kern E. R. 2006; Human cytomegalovirus UL27 is not required for viral replication in human tissue implanted in SCID mice. Virol J 3:18 [View Article][PubMed]
    [Google Scholar]
  59. Quenelle D. C., Collins D. J., Pettway L. R., Hartline C. B., Beadle J. R., Wan W. B., Hostetler K. Y., Kern E. R. 2008; Effect of oral treatment with (S)-HPMPA, HDP-(S)-HPMPA or ODE-(S)-HPMPA on replication of murine cytomegalovirus (MCMV) or human cytomegalovirus (HCMV) in animal models. Antiviral Res 79:133–135 [View Article][PubMed]
    [Google Scholar]
  60. Reynaud J. M., Jégou J. F., Welsch J. C., Horvat B. 2014; Human herpesvirus 6A infection in CD46 transgenic mice: viral persistence in the brain and increased production of proinflammatory chemokines via Toll-like receptor 9. J Virol 88:5421–5436 [View Article][PubMed]
    [Google Scholar]
  61. Rickinson A. B., Kieff E. 2007; Epstein–Barr virus. In Fields Virology, 5th edn. pp. 2655–2700 Edited by Knipe D. M., Howley P. M. Philadelphia, PA: Lippincott Williams & Wilkins;
    [Google Scholar]
  62. Sato K., Misawa N., Nie C., Satou Y., Iwakiri D., Matsuoka M., Takahashi R., Kuzushima K., Ito M.other authors 2011; A novel animal model of Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis in humanized mice. Blood 117:5663–5673 [View Article][PubMed]
    [Google Scholar]
  63. Shope T., Dechairo D., Miller G. 1973; Malignant lymphoma in cottontop marmosets after inoculation with Epstein–Barr virus. Proc Natl Acad Sci U S A 70:2487–2491 [View Article][PubMed]
    [Google Scholar]
  64. Shultz L. D., Ishikawa F., Greiner D. L. 2007; Humanized mice in translational biomedical research. Nat Rev Immunol 7:118–130 [View Article][PubMed]
    [Google Scholar]
  65. Shultz L. D., Saito Y., Najima Y., Tanaka S., Ochi T., Tomizawa M., Doi T., Sone A., Suzuki N.other authors 2010; Generation of functional human T-cell subsets with HLA-restricted immune responses in HLA class I expressing NOD/SCID/IL2rγnull humanized mice. Proc Natl Acad Sci U S A 107:13022–13027 [View Article][PubMed]
    [Google Scholar]
  66. Shultz L. D., Brehm M. A., Garcia-Martinez J. V., Greiner D. L. 2012; Humanized mice for immune system investigation: progress, promise and challenges. Nat Rev Immunol 12:786–798 [View Article][PubMed]
    [Google Scholar]
  67. Smith M. S., Goldman D. C., Bailey A. S., Pfaffle D. L., Kreklywich C. N., Spencer D. B., Othieno F. A., Streblow D. N., Garcia J. V.other authors 2010; Granulocyte-colony stimulating factor reactivates human cytomegalovirus in a latently infected humanized mouse model. Cell Host Microbe 8:284–291 [View Article][PubMed]
    [Google Scholar]
  68. Staudt M. R., Kanan Y., Jeong J. H., Papin J. F., Hines-Boykin R., Dittmer D. P. 2004; The tumor microenvironment controls primary effusion lymphoma growth in vivo. Cancer Res 64:4790–4799 [View Article][PubMed]
    [Google Scholar]
  69. Stevenson P. G., Efstathiou S. 2005; Immune mechanisms in murine gammaherpesvirus-68 infection. Viral Immunol 18:445–456 [View Article][PubMed]
    [Google Scholar]
  70. Strowig T., Gurer C., Ploss A., Liu Y. F., Arrey F., Sashihara J., Koo G., Rice C. M., Young J. W.other authors 2009; Priming of protective T cell responses against virus-induced tumors in mice with human immune system components. J Exp Med 206:1423–1434 [View Article][PubMed]
    [Google Scholar]
  71. Takahashi M., Asano Y., Kamiya H., Baba K., Ozaki T., Otsuka T., Yamanishi K. 2008; Development of varicella vaccine. J Infect Dis 197:Suppl 2S41–S44 [View Article][PubMed]
    [Google Scholar]
  72. Tanner A., Carlson S. A., Nukui M., Murphy E. A., Berges B. K. 2013; Human herpesvirus 6A infection and immunopathogenesis in humanized Rag2–/– γc–/– mice. J Virol 87:12020–12028 [View Article][PubMed]
    [Google Scholar]
  73. Tanner A., Taylor S. E., Decottignies W., Berges B. K. 2014; Humanized mice as a model to study human hematopoietic stem cell transplantation. Stem Cells Dev 23:76–82 [View Article][PubMed]
    [Google Scholar]
  74. Traggiai E., Chicha L., Mazzucchelli L., Bronz L., Piffaretti J. C., Lanzavecchia A., Manz M. G. 2004; Development of a human adaptive immune system in cord blood cell-transplanted mice. Science 304:104–107 [View Article][PubMed]
    [Google Scholar]
  75. Umashankar M., Petrucelli A., Cicchini L., Caposio P., Kreklywich C. N., Rak M., Bughio F., Goldman D. C., Hamlin K. L.other authors 2011; A novel human cytomegalovirus locus modulates cell type-specific outcomes of infection. PLoS Pathog 7:e1002444 [View Article][PubMed]
    [Google Scholar]
  76. Virtanen J. O., Färkkilä M., Multanen J., Uotila L., Jääskeläinen A. J., Vaheri A., Koskiniemi M. 2007; Evidence for human herpesvirus 6 variant A antibodies in multiple sclerosis: diagnostic and therapeutic implications. J Neurovirol 13:347–352 [View Article][PubMed]
    [Google Scholar]
  77. Wahl A., Linnstaedt S. D., Esoda C., Krisko J. F., Martinez-Torres F., Delecluse H. J., Cullen B. R., Garcia J. V. 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 87:5437–5446 [View Article][PubMed]
    [Google Scholar]
  78. Wang W., Taylor S. L., Leisenfelder S. A., Morton R., Moffat J. F., Smirnov S., Zhu H. 2005; Human cytomegalovirus genes in the 15-kilobase region are required for viral replication in implanted human tissues in SCID mice. J Virol 79:2115–2123 [View Article][PubMed]
    [Google Scholar]
  79. Wang L. X., Kang G., Kumar P., Lu W., Li Y., Zhou Y., Li Q., Wood C. 2014; Humanized-BLT mouse model of Kaposi’s sarcoma-associated herpesvirus infection. Proc Natl Acad Sci U S A 111:3146–3151 [View Article][PubMed]
    [Google Scholar]
  80. Washburn M. L., Bility M. T., Zhang L., Kovalev G. I., Buntzman A., Frelinger J. A., Barry W., Ploss A., Rice C. M., Su L. 2011; A humanized mouse model to study hepatitis C virus infection, immune response, and liver disease. Gastroenterology 140:1334–1344 [View Article][PubMed]
    [Google Scholar]
  81. Wedderburn N., Edwards J. M., Desgranges C., Fontaine C., Cohen B., de Thé G. 1984; Infectious mononucleosis-like response in common marmosets infected with Epstein–Barr virus. J Infect Dis 150:878–882 [View Article][PubMed]
    [Google Scholar]
  82. White R. E., Rämer P. C., Naresh K. N., Meixlsperger S., Pinaud L., Rooney C., Savoldo B., Coutinho R., Bödör C.other authors 2012; EBNA3B-deficient EBV promotes B cell lymphomagenesis in humanized mice and is found in human tumors. J Clin Invest 122:1487–1502 [View Article][PubMed]
    [Google Scholar]
  83. Wu W., Rochford R., Toomey L., Harrington W. J. Jr, Feuer G. 2005; Inhibition of HHV-8/KSHV infected primary effusion lymphomas in NOD/SCID mice by azidothymidine and interferon-alpha. Leuk Res 29:545–555 [View Article][PubMed]
    [Google Scholar]
  84. Wu W., Vieira J., Fiore N., Banerjee P., Sieburg M., Rochford R., Harrington W. J. Jr, Feuer G. 2006; KSHV/HHV-8 infection of human hematopoietic progenitor (CD34+) cells: persistence of infection during hematopoiesis in vitro and in vivo. Blood 108:141–151 [View Article][PubMed]
    [Google Scholar]
  85. Yajima M., Imadome K., Nakagawa A., Watanabe S., Terashima K., Nakamura H., Ito M., Shimizu N., Honda M.other authors 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 198:673–682 [View Article][PubMed]
    [Google Scholar]
  86. Yajima M., Imadome K. I., Nakagawa A., Watanabe S., Terashima K., Nakamura H., Ito M., Shimizu N., Yamamoto N., Fujiwara S. 2009; T cell-mediated control of Epstein–Barr virus infection in humanized mice. J Infect Dis 200:1611–1615 [View Article][PubMed]
    [Google Scholar]
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