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.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.067793-0
2014-10-01
2019-11-15
Loading full text...

Full text loading...

/deliver/fulltext/jgv/95/10/2106.html?itemId=/content/journal/jgv/10.1099/vir.0.067793-0&mimeType=html&fmt=ahah

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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][PubMed]
    [Google Scholar]
  36. Lebbé C., Francès C.. ( 2009;). Human herpesvirus 8. . Cancer Treat Res 146:, 169–188. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][PubMed]
    [Google Scholar]
  44. McGregor A.. ( 2010;). Current and new cytomegalovirus antivirals and novel animal model strategies. . Inflamm Allergy Drug Targets 9:, 286–299. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][PubMed]
    [Google Scholar]
  69. Stevenson P. G., Efstathiou S.. ( 2005;). Immune mechanisms in murine gammaherpesvirus-68 infection. . Viral Immunol 18:, 445–456. [CrossRef][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. [CrossRef][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 2), S41–S44. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.067793-0
Loading
/content/journal/jgv/10.1099/vir.0.067793-0
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error