Chapter 19 : Virus-Induced Immunosuppression

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Many laboratories are studying the immunosuppression induced by measles virus (MV) infection. One theory about the mechanism is that the viral infections shift a type 1 immune response to a type 2 immune response. This mechanism was explored further to demonstrate that the interaction of MV with its cellular receptor, CD46, results in the suppression of IL-12 which is required for type 1 immune responses. Another theory about the mechanism is that an as-yet-unidentified soluble factor is able to inhibit lymphoproliferation. Research groups are addressing the role that the MV proteins play in immunosuppression, while examining the role of the alternate MV receptor, signaling lymphocytic activation molecule (SLAM), in immunosuppression. A research group is examining the Fas-mediated apoptosis of MV-infected dendritic cells (DCs) as a means of explaining the presence of both a specific immune response and immunosuppression. Regardless of the extensive work that has been done on MV-induced immunosuppression, the exact molecular mechanism remains unresolved and may be multifactorial.

Citation: Libbey J, Fujinami R. 2002. Virus-Induced Immunosuppression, p 377-387. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch19

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Immune Systems
Infection and Immunity
Tumor Necrosis Factor alpha
Complement System
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MV genome. The structure of the MV RNA and resultant viral proteins is shown.

Citation: Libbey J, Fujinami R. 2002. Virus-Induced Immunosuppression, p 377-387. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch19
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1. Aaby, P. 1988. Malnutrition and overcrowding/ intensive exposure in severe measles infection: review of community studies. Rev. Infect. Dis. 10: 478 491.
2. Aaby, P.,, J. Bukh,, G. Hoff,, J. Leerhoy,, I. M. Lisse,, C. H. Mordhorst,, and I. R. Pedersen. 1986. High measles mortality in infancy related to intensity of exposure. J. Pediatr. 109: 40 44.
3. Aaby, P.,, J. Bukh,, G. Hoff,, I. M. Lisse,, and A. J. Smits. 1987. Humoral immunity in measles infection: a critical factor? Med. Hypotheses 23: 287 301.
4. Aaby, P.,, J. Bukh,, I. M. Lisse,, and A. J. Smits. 1984. Overcrowding and intensive exposure as determinants of measles mortality. Am. J. Epidemiol. 120: 49 63.
5. Aaby, P.,, and J. Leeuwenburg. 1990. Patterns of transmission and severity of measles infection: a reanalysis of data from the Machakos area, Kenya. J. Infect. Dis. 161: 171 174.
6. Aaby, P.,, I. M. Lisse,, K. Molbak,, K. Knudsen,, and H. Whittle. 1996. No persistent T lymphocyte immunosuppression or increased mortality after measles infection: a community study from Guinea-Bissau. Pediatr. Infect. Dis. J. 15: 39 44.
7. Abramson, O.,, R. Dagan,, A. Tal,, and S. Sofer. 1995. Severe complications of measles requiring intensive care in infants and young children. Arch. Pediatr. Adolesc. Med. 149: 1237 1240.
8. Albrecht, P.,, F. A. Ennis,, E. J. Saltzman,, and S. Krugman. 1977. Persistence of maternal antibody in infants beyond 12 months: mechanism of measles vaccine failure. J. Pediatr. 91: 715 718.
9. Bell, A. F.,, J. B. Burns,, and R. S. Fujinami. 1997. Measles virus infection of human T cells modulates cytokine generation and IL-2 receptor alpha chain expression. Virology 232: 241 247.
10. Black, F. L. 1966. Measles endemicity in insular populations: critical community size and its evolutionary implication. J. Theor. Biol. 11: 207 211.
11. Black, F. L. 1989. Measles active and passive immunity in a worldwide perspective. Prog. Med. Virol. 36: 1 33.
12. Bolt, G.,, and I. R. Pedersen. 1998. The role of subtilisin-like proprotein convertases for cleavage of the measles virus fusion glycoprotein in different cell types. Virology 252: 387 398.
13. Bukholm, G.,, K. Modalsli,, and M. Degre. 1986. Effect of measles-virus infection and interferon treatment on invasiveness of Shigella flexneri in HEp2-cell cultures. J. Med. Microbiol. 22: 335 341.
14. Burnet, F. M. 1968. Measles as an index of immunological function. Lancet ii: 610 613.
15. Christensen, P. E.,, H. Schmidt,, H. O. Bang,, V. Andersen,, B. Jordal,, and O. Jensen. 1953. An epidemic of measles in southern Greenland, 1951. Measles in virgin soil. II. The epidemic proper. Acta Med. Scand. 144: 430 449.
16. Coovadia, H. M.,, M. A. Parent,, W. E. Loening,, A. Wesley,, B. Burgess,, F. Hallett,, P. Brain,, J. Grace,, J. Naidoo,, P. M. Smythe,, and G. H. Vos. 1974. An evaluation of factors associated with the depression of immunity in malnutrition and in measles. Am. J. Clin. Nutr. 27: 665 669.
17. Coovadia, H. M.,, A. Wesley,, and P. Brain. 1978. Immunological events in acute measles influencing outcome. Arch. Dis. Child. 53: 861 867.
18. Dorig, R. E.,, A. Marcil,, A. Chopra,, and C. D. Richardson. 1993. The human CD46 molecule is a receptor for measles virus (Edmonston strain). Cell 75: 295 305.
19. Dowdle, W. R.,, and W. A. Orenstein. 1994. Quest for life-long protection by vaccination. Proc. Natl. Acad. Sci. USA 91: 2464 2468.
20. Enders, J. F.,, S. L. Katz,, M. V. Milovanovic,, and A. Holloway. 1960. Studies of an attenuated measles-virus vaccine: I. Development and preparation of the vaccine: technics for assay of effects of vaccination. N. Engl. J. Med. 263: 153 159.
21. Enders, J. F.,, and T. C. Peebles. 1954. Propagation in tissue culture of cytopathic agents from patients with measles. Proc. Soc. Exp. Biol. Med. 86: 277 286.
22. Esolen, L. M.,, S. W. Park,, J. M. Hardwick,, and D. E. Griffin. 1995. Apoptosis as a cause of death in measles virus-infected cells. J. Virol. 69: 3955 3958.
23. Fernandez, H.,, G. Banks,, and R. Smith. 1986. Ribavirin: a clinical overview. Eur. J. Epidemiol. 2: 1 14.
24. Fireman, P.,, G. Friday,, and J. Kumate. 1969. Effect of measles vaccine on immunologic responsiveness. Pediatrics 43: 264 272.
25. Fugier-Vivier, I.,, C. Servet-Delprat,, P. Rivailler,, M. C. Rissoan,, Y. J. Liu,, and C. Rabourdin-Combe. 1997. Measles virus suppresses cell-mediated immunity by interfering with the survival and functions of dendritic and T cells. J. Exp. Med. 186: 813 823.
26. Fujinami, R. S.,, and M. B. A. Oldstone. 1981. Failure to cleave measles virus fusion protein in lymphoid cells. J. Exp. Med. 154: 1489 1499.
27. Fujinami, R. S.,, X. Sun,, J. M. Howell,, J. C. Jenkin,, and J. B. Burns. 1998. Modulation of immune system function by measles virus infection: role of soluble factor and direct infection. J. Virol. 72: 9421 9427.
28. Garenne, M.,, and P. Aaby. 1990. Pattern of exposure and measles mortality in Senegal. J. Infect. Dis. 161: 1088 1094.
29. Gavish, D.,, Y. Kleinman,, A. Morag,, and T. Chajek-Shaul. 1983. Hepatitis and jaundice associated with measles in young adults. An analysis of 65 cases. Arch. Intern. Med. 143: 674 677.
30. Goldenberger, J.,, and J. F. Anderson. 1911. An experimental demonstration of the presence of the virus of measles in the mixed buccal and nasal secretions. JAMA 57: 496 578.
31. Greenberg, S. B. 1991. Viral pneumonia. Infect. Dis. Clin. N. Am. 5: 603 621.
32. Griffin, D. E. 1995. Immune responses during measles virus infection. Curr. Top. Microbiol. Immunol. 191: 117 134.
33. Griffin, D. E.,, and W. J. Bellini,. 1996. Measles virus, p. 1267 1312. In B. N. Fields,, D. M. Knipe,, and P. M. Howley (ed.), Fields Virology, 3rd ed. Lippincott-Raven Publishers, Philadelphia, Pa.
34. Griffin, D. E.,, and B. J. Ward. 1993. Differential CD4 T cell activation in measles. J. Infect. Dis. 168: 275 281.
35. Griffin, D. E.,, B. J. Ward,, and L. M. Esolen. 1994. Pathogenesis of measles virus infection: an hypothesis for altered immune responses. J. Infect. Dis. 170( Suppl. 1): S24 S31.
36. Griffin, D. E.,, B. J. Ward,, E. Jauregui,, R. T. Johnson,, and A. Vaisberg. 1989. Immune activation in measles. N. Engl. J. Med. 320: 1667 1672.
37. Griffin, D. E.,, B. J. Ward,, E. Jauregui,, R. T. Johnson,, and A. Vaisberg. 1990. Immune activation during measles: interferon-γ and neopterin in plasma and cerebrospinal fluid in complicated and uncomplicated disease. J. Infect. Dis. 161: 449 453.
38. Griffin, D. E.,, B. J. Ward,, E. Jauregui,, R. T. Johnson,, and A. Vaisberg. 1990. Natural killer cell activity during measles. Clin. Exp. Immunol. 81: 218 224.
39. Griffin, D. E.,, B. J. Ward,, E. Juaregui,, R. T. Johnson,, and A. Vaisberg. 1992. Immune activation during measles: β 2-microglobulin in plasma and cerebrospinal fluid in complicated and uncomplicated disease. J. Infect. Dis. 166: 1170 1173.
40. Hirsch, R. L.,, D. E. Griffin,, R. T. Johnson,, S. J. Cooper,, I. Lindo de Soriano,, S. Roedenbeck,, and A. Vaisberg. 1984. Cellular immune responses during complicated and uncomplicated measles virus infections of man. Clin. Immunol. Immunopathol. 31: 1 12.
41. Hsu, E. C.,, C. Iorio,, F. Sarangi,, A. A. Khine,, and C. D. Richardson. 2001. CDw 150(SLAM) is a receptor for a lymphotropic strain of measles virus and may account for the immunosuppressive properties of this virus. Virology 279: 9 21.
42. Kaplan, L. J.,, R. S. Daum,, M. Smaron,, and C. A. McCarthy. 1992. Severe measles in immunocompromised patients. JAMA 267: 1237 1241.
43. Karp, C. L. 1999. Measles: immunosuppression, interleukin-12, and complement receptors. Immunol. Rev. 168: 91 101.
44. Karp, C. L.,, and M. Wills-Karp. 2001. Complement and IL-12: yin and yang. Microb. Infect. 3: 109 119.
45. Karp, C. L.,, M. Wysocka,, L. M. Wahl,, J. M. Ahearn,, P. J. Cuomo,, B. Sherry,, G. Trinchieri,, and D. E. Griffin. 1996. Mechanism of suppression of cell-mediated immunity by measles virus. Science 273: 228 231.
46. Kiepiela, P.,, H. M. Coovadia,, and P. Coward. 1987. T helper cell defect related to severity in measles. Scand. J. Infect. Dis. 19: 185 192.
47. Kipps, A.,, L. Stern,, and E. G. Vaughan. 1966. The duration and the possible significance of the depression of tuberculin sensitivity following measles. S. Afr. Med. J. 40: 104 108.
48. Klagge, I. M.,, V. ter Meulen,, and S. Schneider- Schaulies. 2000. Measles virus-induced promotion of dendritic cell maturation by soluble mediators does not overcome the immunosuppressive activity of viral glycoproteins on the cell surface. Eur. J. Immunol. 30: 2741 2750.
49. Kobune, F.,, H. Sakata,, and A. Sugiura. 1990. Marmoset lymphoblastoid cells as a sensitive host for isolation of measles virus. J. Virol. 64: 700 705.
50. Krakowka, S.,, R. J. Higgins,, and A. Koestner. 1980. Canine distemper virus: review of structural and functional modulations in lymphoid tissues. Am. J. Vet. Res. 41: 284 292.
51. Krugman, S. 1963. Medical progress: the clinical use of gamma globulin. N. Engl. J. Med. 269: 195 201.
52. Lamb, R. A.,, and D. Kolakofsky,. 1996. Paramyxoviridae: the viruses and their replication, p. 1177 1204. In B. N. Fields,, D. M. Knipe,, and P. M. Howley (ed.), Fields Virology, 3rd ed. Lippincott- Raven Publishers, Philadelphia, Pa.
53. Liszewski, M. K.,, T. W. Post,, and J. P. Atkinson. 1991. Membrane cofactor protein (MCP or CD46): newest member of the regulators of complement activation gene cluster. Annu. Rev. Immunol. 9: 431 455.
54. Lucas, J. 1790. An account of uncommon symptoms succeeding the measles; with additional remarks on the infection of measles and smallpox. Lond. Med. J. 11: 325 331.
55. Marie, J. C.,, J. Kehren,, M. C. Trescol- Biemont,, A. Evlashev,, H. Valentin,, T. Walzer,, R. Tedone,, B. Loveland,, J. F. Nicolas,, C. Rabourdin-Combe,, and B. Horvat. 2001. Mechanism of measles virus-induced suppression of inflammatory immune responses. Immunity 14: 69 79.
56. Mason, W. H. 1995. Measles. Adolesc. Med. 6: 1 14.
57. McChesney, M. B.,, A. Altman,, and M. B. A. Oldstone. 1988. Suppression of T lymphocyte function by measles virus is due to cell cycle arrest in G1. J. Immunol. 140: 1269 1273.
58. McChesney, M. B.,, R. S. Fujinami,, N. W. Lerche,, P. A. Marx,, and M. B. A. Oldstone. 1989. Virus-induced immunosuppression: infection of peripheral blood mononuclear cells and suppression of immunoglobulin synthesis during natural measles virus infection of rhesus monkeys. J. Infect. Dis. 159: 757 760.
59. McChesney, M. B.,, J. H. Kehrl,, A. Valsamakis,, A. S. Fauci,, and M. B. A. Oldstone. 1987. Measles virus infection of B lymphocytes permits cellular activation but blocks progression through the cell cycle. J. Virol. 61: 3441 3447.
60. McChesney, M. B.,, and M. B. A. Oldstone. 1989. Virus-induced immunosuppression: infections with measles virus and human immunodeficiency virus. Adv. Immunol. 45: 335 380.
61. Mosser, D. M.,, and C. L. Karp. 1999. Receptor mediated subversion of macrophage cytokine production by intracellular pathogens. Curr. Opin. Immunol. 11: 406 411.
62. Naniche, D.,, S. I. Reed,, and M. B. A. Oldstone. 1999. Cell cycle arrest during measles virus infection: a G0-like block leads to suppression of retinoblastoma protein expression. J. Virol. 73: 1894 1901.
63. Naniche, D.,, G. Varior-Krishnan,, F. Cervoni,, T. F. Wild,, B. Rossi,, C. Rabourdin- Combe,, and D. Gerlier. 1993. Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus. J. Virol. 67: 6025 6032.
64. Norrby, E.,, H. Sheshberadaran,, K. C. Mc- Cullough,, W. C. Carpenter,, and C. Orvell. 1985. Is rinderpest virus the archevirus of the Morbillivirus genus? Intervirology 23: 228 232.
65. Omer, M. I. 1999. Measles: a disease that has to be eradicated. Ann. Trop. Paediatr. 19: 125 134.
66. Orenstein, W. A.,, P. M. Strebel,, M. Papania,, R. W. Sutter,, W. J. Bellini,, and S. L. Cochi. 2000. Measles eradication: is it in our future? Am. J. Public Health 90: 1521 1525.
67. Osler, W. 1904. The Principles and Practices of Medicine, 5th ed., p. 88. D. Appleton and Company, New York, N.Y.
68. Panum, P. 1938. Observations made during the epidemic of measles on the Faroe Islands in the year 1846. Med. Classics 3: 829 886.
69. Patterson, J. B.,, M. Manchester,, and M. B. A. Oldstone. 2001. Disease model: dissecting the pathogenesis of the measles virus. Trends Mol. Med. 7: 85 88.
70. Perry, K. R.,, D. W. Brown,, J. V. Parry,, S. Panday,, C. Pipkin,, and A. Richards. 1993. Detection of measles, mumps, and rubella antibodies in saliva using antibody capture radioimmunoassay. J. Med. Virol. 40: 235 240.
71. Plotkin, S. A. 1967. Vaccination against measles in the 18th century. Clin. Pediatr. 6: 312 315.
72. Rima, B.,, D. J. Alexander,, M. A. Billeter,, P. L. Collins,, D. W. Kingsbury,, M. A. Lipkind,, Y. Nagai,, C. Orvell,, C. R. Pringle,, and V. ter Meulen,. 1995. Paramyxovirus taxonomy, p. 268 274. In F. A. Murphy,, C. M. Fauquet,, D. H. L. Bishop,, S. A. Ghabiral,, A. W. Jarvis,, G. P. Martelli,, M. A. Mayo,, and M. D. Summers (ed.), Virus Taxonomy. Sixth Report of the International Committee on Taxonomy of Viruses. Springer-Verlag Publishers, New York, N.Y.
73. Ross, L. A.,, K. S. Kim,, W. H. Mason, Jr.,, and E. Gomperts. 1990. Successful treatment of disseminated measles in a patient with acquired immunodeficiency syndrome: consideration of antiviral and passive immunotherapy. Am. J. Med. 88: 313 314.
74. Rossier, E.,, H. Miller,, B. McCulloch,, L. Sullivan,, and K. Ward. 1991. Comparison of immunofluorescence and enzyme immunoassay for detection of measles-specific immunoglobulin M antibody. J. Clin. Microbiol. 29: 1069 1071.
75. Sanchez-Lanier, M.,, P. Guerin,, L. C. McLaren,, and A. D. Bankhurst. 1988. Measles virus-induced suppression of lymphocyte proliferation. Cell. Immunol. 116: 367 381.
76. Schlender, J.,, J. J. Schnorr,, P. Spielhoffer,, T. Cathomen,, R. Cattaneo,, M. A. Billeter,, V. ter Meulen,, and S. Schneider-Schaulies. 1996. Interaction of measles virus glycoproteins with the surface of uninfected peripheral blood lymphocytes induces immunosuppression in vitro. Proc. Natl. Acad. Sci. USA 93: 13194 13199.
77. Schwarz, A. J. F. 1962. Preliminary tests of a highly attenuated measles vaccine. Am. J. Dis. Child. 103: 216 219.
78. Servet-Delprat, C.,, P. O. Vidalain,, O. Azocar,, F. Le Deist,, A. Fischer,, and C. Rabourdin- Combe. 2000. Consequences of Fas-mediated human dendritic cell apoptosis induced by measles virus. J. Virol. 74: 4387 4393.
79. Siber, G. R.,, B. G. Werner,, N. A. Halsey,, R. Reid,, J. Almeido-Hill,, S. C. Garrett,, C. Thompson,, and M. Santosham. 1993. Interference of immune globulin with measles and rubella immunization. J. Pediatr. 122: 204 211.
80. Stogner, S. W.,, J. W. King,, C. Black-Payne,, and J. Bocchini. 1993. Ribavirin and intravenous immune globulin therapy for measles pneumonia in HIV infection. South Med. J. 86: 1415 1418.
81. Sun, X.,, J. B. Burns,, J. M. Howell,, and R. S. Fujinami. 1998. Suppression of antigen-specific T cell proliferation by measles virus infection: role of a soluble factor in suppression. Virology 246: 24 33.
82. Tatsuo, H.,, N. Ono,, K. Tanaka,, and Y. Yanagi. 2000. SLAM (CDw150) is a cellular receptor for measles virus. Nature 406: 893 897.
83. Tulchinsky, T. H.,, G. M. Ginsberg,, Y. Abed,, M. T. Angeles,, C. Akukwe,, and J. Bonn. 1993. Measles control in developing and developed countries: the case for a two-dose policy. Bull. W. H. O. 71: 93 103.
84. von Pirquet, C. 1908. Verhalten der kutanen tuberkulin-reaktion wahrend der Masern. Dtsch. Med. Wochenschr. 34: 1297 1300.
85. Ward, B. J.,, and D. E. Griffin. 1993. Changes in cytokine production after measles virus vaccination: predominant production of IL-4 suggests induction of a Th2 response. Clin. Immunol. Immunopathol. 67: 171 177.
86. Ward, B. J.,, R. T. Johnson,, A. Vaisberg,, E. Jauregui,, and D. E. Griffin. 1990. Spontaneous proliferation of peripheral mononuclear cells in natural measles virus infection: identification of dividing cells and correlation with mitogen responsiveness. Clin. Immunol. Immunopathol. 55: 315 326.
87. Ward, B. J.,, R. T. Johnson,, A. Vaisberg,, E. Jauregui,, and D. E. Griffin. 1991. Cytokine production in vitro and the lymphoproliferative defect of natural measles virus infection. Clin. Immunol. Immunopathol. 61: 236 248.
88. Warner, J. O.,, and W. C. Marshall. 1976. Crippling lung disease after measles and adenovirus infection. Br. J. Dis. Chest 70: 89 94.
89. Watanabe, M.,, A. Hirano,, S. Stenglein,, J. Nelson,, G. Thomas,, and T. C. Wong. 1995. Engineered serine protease inhibitor prevents furin- catalyzed activation of the fusion glycoprotein and production of infectious measles virus. J. Virol. 69: 3206 3210.
90. White, D. O.,, and F. J. Fenner. 1994. Paramyxoviridae, p. 456 474. Medical Virology, 4th ed. Academic Press, San Diego, Calif.
91. Whittle, H. C.,, A. Bradley-Moore,, A. Fleming,, and B. M. Greenwood. 1973. Effects of measles on the immune response of Nigerian children. Arch. Dis. Child. 48: 753 756.
92. Whittle, H. C.,, J. S. Smith,, O. I. Kogbe,, J. Dossetor,, and M. Duggan. 1979. Severe ulcerative herpes of mouth and eye following measles. Trans. R. Soc. Trop. Med. Hyg. 73: 66 69.
93. Yanagi, Y. 2001. The cellular receptor for measles virus—elusive no more. Rev. Med. Virol. 11: 149 156.
94. Yetgin, S.,, and C. Altay. 1980. Defective bactericidal function of polymorphonuclear neutrophils in children with measles. Acta Paediatr. Scand. 69: 411 413.
95. Yoshioka, K.,, H. Miyata,, and S. Maki. 1981. Transient remission of juvenile rheumatoid arthritis after measles. Acta Paediatr. Scand. 70: 419 420.


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Potential mechanisms of MV-induced immunosuppression

Citation: Libbey J, Fujinami R. 2002. Virus-Induced Immunosuppression, p 377-387. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch19

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