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. 1996 Jun;70(6):3734–3740. doi: 10.1128/jvi.70.6.3734-3740.1996

Measles virus infection of thymic epithelium in the SCID-hu mouse leads to thymocyte apoptosis.

P G Auwaerter 1, H Kaneshima 1, J M McCune 1, G Wiegand 1, D E Griffin 1
PMCID: PMC190249  PMID: 8648708

Abstract

Mortality from measles is caused mostly by secondary infections associated with the depression of cellular immunity. The mechanism of immune suppression and the role of virus strain differences on the immune system are incompletely understood. SCID-hu mice were used to determine the effects of virulent, wild-type (Chicago-1) and avirulent, vaccine (Moraten) strains of measles virus (MV) on the human thymus in vivo. Chicago-1 replicated rapidly, with a 100-fold decrease in numbers of thymocytes, whereas Moraten replicated slowly, without significant thymocyte death. Productive MV infection occurred not in thymocytes but in thymic epithelial and myelomonocytic cells. Wild-type MV infection of thymic stromata leads to induction of thymocyte apoptosis and may contribute to a long-term alteration of immune responses. The extent of thymic disruption reflects the virulence of the virus, and therefore the SCID-hu mouse may serve as the first small animal model for the study of MV pathogenesis.

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Selected References

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  1. Albrecht P., Herrmann K., Burns G. R. Role of virus strain in conventional and enhanced measles plaque neutralization test. J Virol Methods. 1981 Dec;3(5):251–260. doi: 10.1016/0166-0934(81)90062-8. [DOI] [PubMed] [Google Scholar]
  2. Aldrovandi G. M., Feuer G., Gao L., Jamieson B., Kristeva M., Chen I. S., Zack J. A. The SCID-hu mouse as a model for HIV-1 infection. Nature. 1993 Jun 24;363(6431):732–736. doi: 10.1038/363732a0. [DOI] [PubMed] [Google Scholar]
  3. Arneborn P., Biberfeld G. T-lymphocyte subpopulations in relation to immunosuppression in measles and varicella. Infect Immun. 1983 Jan;39(1):29–37. doi: 10.1128/iai.39.1.29-37.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Athanassious R., Brunet M., Lussier G. Ultrastructural study of mouse thymus virus replication. Acta Virol. 1993 Apr-Jun;37(2-3):175–180. [PubMed] [Google Scholar]
  5. Auwaerter P. G., Hussey G. D., Goddard E. A., Hughes J., Ryon J. J., Strebel P. M., Beatty D., Griffin D. E. Changes within T cell receptor V beta subsets in infants following measles vaccination. Clin Immunol Immunopathol. 1996 May;79(2):163–170. doi: 10.1006/clin.1996.0063. [DOI] [PubMed] [Google Scholar]
  6. Axton J. H. Measles and the state of nutrition. S Afr Med J. 1979 Jan 27;55(4):125–126. [PubMed] [Google Scholar]
  7. BUNTING C. H. The giant-cells of measles. Yale J Biol Med. 1950 Jul;22(6):513–519. [PMC free article] [PubMed] [Google Scholar]
  8. Beckford A. P., Kaschula R. O., Stephen C. Factors associated with fatal cases of measles. A retrospective autopsy study. S Afr Med J. 1985 Dec 7;68(12):858–863. [PubMed] [Google Scholar]
  9. Bhatia S. K., Tygrett L. T., Grabstein K. H., Waldschmidt T. J. The effect of in vivo IL-7 deprivation on T cell maturation. J Exp Med. 1995 Apr 1;181(4):1399–1409. doi: 10.1084/jem.181.4.1399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bonyhadi M. L., Rabin L., Salimi S., Brown D. A., Kosek J., McCune J. M., Kaneshima H. HIV induces thymus depletion in vivo. Nature. 1993 Jun 24;363(6431):728–732. doi: 10.1038/363728a0. [DOI] [PubMed] [Google Scholar]
  11. Chino F., Kodama H., Ohkawa T., Egashira Y. Alterations of the thymus and peripheral lymphoid tissues in fatal measles. A review of 14 autopsy cases. Acta Pathol Jpn. 1979 May;29(3):493–507. doi: 10.1111/j.1440-1827.1979.tb00205.x. [DOI] [PubMed] [Google Scholar]
  12. Cohen J. J. Glucocorticoid-induced apoptosis in the thymus. Semin Immunol. 1992 Dec;4(6):363–369. [PubMed] [Google Scholar]
  13. Esolen L. M., Park S. W., Hardwick J. M., Griffin D. E. Apoptosis as a cause of death in measles virus-infected cells. J Virol. 1995 Jun;69(6):3955–3958. doi: 10.1128/jvi.69.6.3955-3958.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Esolen L. M., Ward B. J., Moench T. R., Griffin D. E. Infection of monocytes during measles. J Infect Dis. 1993 Jul;168(1):47–52. doi: 10.1093/infdis/168.1.47. [DOI] [PubMed] [Google Scholar]
  15. Gavrieli Y., Sherman Y., Ben-Sasson S. A. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol. 1992 Nov;119(3):493–501. doi: 10.1083/jcb.119.3.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Griebel P. J., Ohmann H. B., Lawman M. J., Babiuk L. A. The interaction between bovine herpesvirus type 1 and activated bovine T lymphocytes. J Gen Virol. 1990 Feb;71(Pt 2):369–377. doi: 10.1099/0022-1317-71-2-369. [DOI] [PubMed] [Google Scholar]
  17. Griffin D. E., Ward B. J. Differential CD4 T cell activation in measles. J Infect Dis. 1993 Aug;168(2):275–281. doi: 10.1093/infdis/168.2.275. [DOI] [PubMed] [Google Scholar]
  18. Hardwick J. M., Bussell R. H. Glycoproteins of measles virus under reducing and nonreducing conditions. J Virol. 1978 Feb;25(2):687–692. doi: 10.1128/jvi.25.2.687-692.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Henderson R. H., Keja J., Hayden G., Galazka A., Clements J., Chan C. Immunizing the children of the world: progress and prospects. Bull World Health Organ. 1988;66(5):535–543. [PMC free article] [PubMed] [Google Scholar]
  20. Inoue M., Fukuda M., Miyano K. Thymic lesions in chicken infected with infectious bursal disease virus. Avian Dis. 1994 Oct-Dec;38(4):839–846. [PubMed] [Google Scholar]
  21. Jeurissen S. H., Wagenaar F., Pol J. M., van der Eb A. J., Noteborn M. H. Chicken anemia virus causes apoptosis of thymocytes after in vivo infection and of cell lines after in vitro infection. J Virol. 1992 Dec;66(12):7383–7388. doi: 10.1128/jvi.66.12.7383-7388.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kaneshima H., Su L., Bonyhadi M. L., Connor R. I., Ho D. D., McCune J. M. Rapid-high, syncytium-inducing isolates of human immunodeficiency virus type 1 induce cytopathicity in the human thymus of the SCID-hu mouse. J Virol. 1994 Dec;68(12):8188–8192. doi: 10.1128/jvi.68.12.8188-8192.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kobune F., Sakata H., Sugiura A. Marmoset lymphoblastoid cells as a sensitive host for isolation of measles virus. J Virol. 1990 Feb;64(2):700–705. doi: 10.1128/jvi.64.2.700-705.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Krowka J. F., Sarin S., Namikawa R., McCune J. M., Kaneshima H. Human T cells in the SCID-hu mouse are phenotypically normal and functionally competent. J Immunol. 1991 Jun 1;146(11):3751–3756. [PubMed] [Google Scholar]
  25. Liebert U. G., Finke D. Measles virus infections in rodents. Curr Top Microbiol Immunol. 1995;191:149–166. doi: 10.1007/978-3-642-78621-1_10. [DOI] [PubMed] [Google Scholar]
  26. MILLER D. L. FREQUENCY OF COMPLICATIONS OF MEASLES, 1963. REPORT ON A NATIONAL INQUIRY BY THE PUBLIC HEALTH LABORATORY SERVICE IN COLLABORATION WITH THE SOCIETY OF MEDICAL OFFICERS OF HEALTH. Br Med J. 1964 Jul 11;2(5401):75–78. doi: 10.1136/bmj.2.5401.75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. McCune J. M., Namikawa R., Kaneshima H., Shultz L. D., Lieberman M., Weissman I. L. The SCID-hu mouse: murine model for the analysis of human hematolymphoid differentiation and function. Science. 1988 Sep 23;241(4873):1632–1639. doi: 10.1126/science.241.4873.1632. [DOI] [PubMed] [Google Scholar]
  28. McCune J. M., Namikawa R., Shih C. C., Rabin L., Kaneshima H. Suppression of HIV infection in AZT-treated SCID-hu mice. Science. 1990 Feb 2;247(4942):564–566. doi: 10.1126/science.2300816. [DOI] [PubMed] [Google Scholar]
  29. Mocarski E. S., Bonyhadi M., Salimi S., McCune J. M., Kaneshima H. Human cytomegalovirus in a SCID-hu mouse: thymic epithelial cells are prominent targets of viral replication. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):104–108. doi: 10.1073/pnas.90.1.104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Moench T. R., Griffin D. E., Obriecht C. R., Vaisberg A. J., Johnson R. T. Acute measles in patients with and without neurological involvement: distribution of measles virus antigen and RNA. J Infect Dis. 1988 Aug;158(2):433–442. doi: 10.1093/infdis/158.2.433. [DOI] [PubMed] [Google Scholar]
  31. Moffat J. F., Stein M. D., Kaneshima H., Arvin A. M. Tropism of varicella-zoster virus for human CD4+ and CD8+ T lymphocytes and epidermal cells in SCID-hu mice. J Virol. 1995 Sep;69(9):5236–5242. doi: 10.1128/jvi.69.9.5236-5242.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Murphy K. M., Heimberger A. B., Loh D. Y. Induction by antigen of intrathymic apoptosis of CD4+CD8+TCRlo thymocytes in vivo. Science. 1990 Dec 21;250(4988):1720–1723. doi: 10.1126/science.2125367. [DOI] [PubMed] [Google Scholar]
  33. NII S., KAMAHORA J., MORI Y., TAKAHASHI M., NISHIMURA S., OKUNO Y. EXPERIMENTAL PATHOLOGY OF MEASLES IN MONKEYS. Biken J. 1964 Jan;6:271–297. [PubMed] [Google Scholar]
  34. Namikawa R., Kaneshima H., Lieberman M., Weissman I. L., McCune J. M. Infection of the SCID-hu mouse by HIV-1. Science. 1988 Dec 23;242(4886):1684–1686. doi: 10.1126/science.3201256. [DOI] [PubMed] [Google Scholar]
  35. Namikawa R., Weilbaecher K. N., Kaneshima H., Yee E. J., McCune J. M. Long-term human hematopoiesis in the SCID-hu mouse. J Exp Med. 1990 Oct 1;172(4):1055–1063. doi: 10.1084/jem.172.4.1055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Naniche D., Varior-Krishnan G., Cervoni F., Wild T. F., Rossi B., Rabourdin-Combe C., Gerlier D. Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus. J Virol. 1993 Oct;67(10):6025–6032. doi: 10.1128/jvi.67.10.6025-6032.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Naniche D., Wild T. F., Rabourdin-Combe C., Gerlier D. Measles virus haemagglutinin induces down-regulation of gp57/67, a molecule involved in virus binding. J Gen Virol. 1993 Jun;74(Pt 6):1073–1079. doi: 10.1099/0022-1317-74-6-1073. [DOI] [PubMed] [Google Scholar]
  38. Nozawa Y., Ono N., Abe M., Sakuma H., Wakasa H. An immunohistochemical study of Warthin-Finkeldey cells in measles. Pathol Int. 1994 Jun;44(6):442–447. doi: 10.1111/j.1440-1827.1994.tb01708.x. [DOI] [PubMed] [Google Scholar]
  39. Numazaki K., Goldman H., Wong I., Wainberg M. A. Replication of measles virus in cultured human thymic epithelial cells. J Med Virol. 1989 Jan;27(1):52–58. doi: 10.1002/jmv.1890270112. [DOI] [PubMed] [Google Scholar]
  40. Sakaguchi M., Yoshikawa Y., Yamanouchi K., Sata T., Nagashima K., Takeda K. Growth of measles virus in epithelial and lymphoid tissues of cynomolgus monkeys. Microbiol Immunol. 1986;30(10):1067–1073. doi: 10.1111/j.1348-0421.1986.tb03036.x. [DOI] [PubMed] [Google Scholar]
  41. Samsi T. K., Ruspandji T., Susanto I., Gunawan K. Risk factors for severe measles. Southeast Asian J Trop Med Public Health. 1992 Sep;23(3):497–503. [PubMed] [Google Scholar]
  42. Schneider-Schaulies J., Dunster L. M., Kobune F., Rima B., ter Meulen V. Differential downregulation of CD46 by measles virus strains. J Virol. 1995 Nov;69(11):7257–7259. doi: 10.1128/jvi.69.11.7257-7259.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Sellins K. S., Cohen J. J. Gene induction by gamma-irradiation leads to DNA fragmentation in lymphocytes. J Immunol. 1987 Nov 15;139(10):3199–3206. [PubMed] [Google Scholar]
  44. Smith C. A., Williams G. T., Kingston R., Jenkinson E. J., Owen J. J. Antibodies to CD3/T-cell receptor complex induce death by apoptosis in immature T cells in thymic cultures. Nature. 1989 Jan 12;337(6203):181–184. doi: 10.1038/337181a0. [DOI] [PubMed] [Google Scholar]
  45. Stanley S. K., McCune J. M., Kaneshima H., Justement J. S., Sullivan M., Boone E., Baseler M., Adelsberger J., Bonyhadi M., Orenstein J. Human immunodeficiency virus infection of the human thymus and disruption of the thymic microenvironment in the SCID-hu mouse. J Exp Med. 1993 Oct 1;178(4):1151–1163. doi: 10.1084/jem.178.4.1151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Su L., Kaneshima H., Bonyhadi M., Salimi S., Kraft D., Rabin L., McCune J. M. HIV-1-induced thymocyte depletion is associated with indirect cytopathogenicity and infection of progenitor cells in vivo. Immunity. 1995 Jan;2(1):25–36. doi: 10.1016/1074-7613(95)90076-4. [DOI] [PubMed] [Google Scholar]
  47. Ward B. J., Johnson R. T., Vaisberg A., Jauregui E., Griffin D. E. Spontaneous proliferation of peripheral mononuclear cells in natural measles virus infection: identification of dividing cells and correlation with mitogen responsiveness. Clin Immunol Immunopathol. 1990 May;55(2):315–326. doi: 10.1016/0090-1229(90)90107-2. [DOI] [PubMed] [Google Scholar]
  48. White R. G., Boyd J. F. The effect of measles on the thymus and other lymphoid tissues. Clin Exp Immunol. 1973 Mar;13(3):343–357. [PMC free article] [PubMed] [Google Scholar]
  49. Yamanouchi K., Chino F., Kobune F., Kodama H., Tsuruhara T. Growth of measles virus in the lymphoid tissues of monkeys. J Infect Dis. 1973 Dec;128(6):795–799. doi: 10.1093/infdis/128.6.795. [DOI] [PubMed] [Google Scholar]
  50. van Binnendijk R. S., van der Heijden R. W., Osterhaus A. D. Monkeys in measles research. Curr Top Microbiol Immunol. 1995;191:135–148. doi: 10.1007/978-3-642-78621-1_9. [DOI] [PubMed] [Google Scholar]
  51. van Ewijk W. T-cell differentiation is influenced by thymic microenvironments. Annu Rev Immunol. 1991;9:591–615. doi: 10.1146/annurev.iy.09.040191.003111. [DOI] [PubMed] [Google Scholar]

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