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Science 12 July 1996:
Vol. 273. no. 5272, pp. 228 - 231
DOI: 10.1126/science.273.5272.228
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Reports

Mechanism of Suppression of Cell-Mediated Immunity by Measles Virus

Christopher L. Karp, * Maria Wysocka, Larry M. Wahl, Joseph M. Ahearn, Peter J. Cuomo, Barbara Sherry, Giorgio Trinchieri, Diane E. Griffin

The mechanisms underlying the profound suppression of cell-mediated immunity (CMI) accompanying measles are unclear. Interleukin-12 (IL-12), derived principally from monocytes and macrophages, is critical for the generation of CMI. Measles virus (MV) infection of primary human monocytes specifically down-regulated IL-12 production. Cross-linking of CD46, a complement regulatory protein that is the cellular receptor for MV, with antibody or with the complement activation product C3b similarly inhibited monocyte IL-12 production, providing a plausible mechanism for MV-induced immunosuppression. CD46 provides a regulatory link between the complement system and cellular immune responses.

C. L. Karp, J. M. Ahearn, P. J. Cuomo, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
M. Wysocka and G. Trinchieri, Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104, USA.
L. M. Wahl, Laboratory of Immunology, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892, USA.
B. Sherry, Picower Institute for Medical Research, Manhasset, NY 11030, USA.
D. E. Griffin, Department of Molecular Microbiology and Immunology, Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD 21205, USA.
* To whom correspondence should be addressed.


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Measles Virus Induces Functional TRAIL Production by Human Dendritic Cells.
P.-O. Vidalain, O. Azocar, B. Lamouille, A. Astier, C. Rabourdin-Combe, and C. Servet-Delprat (2000)
J. Virol. 74, 556-559
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Cd47 Ligation Selectively Downregulates Human Interleukin 12 Production.
M. Armant, M.-N. Avice, P. Hermann, M. Rubio, M. Kiniwa, G. Delespesse, and M. Sarfati (1999)
J. Exp. Med. 190, 1175-1182
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Murine Gammaherpesvirus 68 Encodes a Functional Regulator of Complement Activation.
S. B. Kapadia, H. Molina, V. van Berkel, S. H. Speck, and H. W. Virgin IV (1999)
J. Virol. 73, 7658-7670
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Measles virus-induced immunosuppression in cotton rats is associated with cell cycle retardation in uninfected lymphocytes.
S. Niewiesk, H. Ohnimus, J.-J. Schnorr, M. Götzelmann, S. Schneider-Schaulies, C. Jassoy, and V. ter Meulen (1999)
J. Gen. Virol. 80, 2023-2029
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Measles virus-induced immunosuppression in vitro is associated with deregulation of G(1) cell cycle control proteins.
O Engelking, L. Fedorov, R Lilischkis, V ter Meulen, and S Schneider-Schaulies (1999)
J. Gen. Virol. 80, 1599-1608
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Human CD46 Enhances Nitric Oxide Production in Mouse Macrophages in Response to Measles Virus Infection in the Presence of Gamma Interferon: Dependence on the CD46 Cytoplasmic Domains.
A. Hirano, Z. Yang, Y. Katayama, J. Korte-Sarfaty, and T. C. Wong (1999)
J. Virol. 73, 4776-4785
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IL-12, IFN-{gamma}, and T Cell Proliferation to Measles in Immunized Infants.
H. A. Gans, Y. Maldonado, L. L. Yasukawa, J. Beeler, S. Audet, M. M. Rinki, R. DeHovitz, and A. M. Arvin (1999)
J. Immunol. 162, 5569-5575
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Impaired T Cell Proliferation in Acute Dengue Infection.
A. Mathew, I. Kurane, S. Green, D. W. Vaughn, S. Kalayanarooj, S. Suntayakorn, F. A. Ennis, and A. L. Rothman (1999)
J. Immunol. 162, 5609-5615
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Requirements for Measles Virus Induction of RANTES Chemokine in Human Astrocytoma-Derived U373 Cells.
K. H. Noe, C. Cenciarelli, S. A. Moyer, P. A. Rota, and M. L. Shin (1999)
J. Virol. 73, 3117-3124
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Cell Cycle Arrest during Measles Virus Infection: a G0-Like Block Leads to Suppression of Retinoblastoma Protein Expression.
D. Naniche, S. I. Reed, and M. B. A. Oldstone (1999)
J. Virol. 73, 1894-1901
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Measles Virus Infection Induces Terminal Differentiation of Human Thymic Epithelial Cells.
H. Valentin, O. Azocar, B. Horvat, R. Williems, R. Garrone, A. Evlashev, M. L. Toribio, and C. Rabourdin-Combe (1999)
J. Virol. 73, 2212-2221
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Measles Virus Infection Synergizes with IL-4 in IgE Class Switching.
F. Imani, D. Proud, and D. E. Griffin (1999)
J. Immunol. 162, 1597-1602
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Suppression of Host Immune Response by the Core Protein of Hepatitis C Virus: Possible Implications for Hepatitis C Virus Persistence.
M. K. Large, D. J. Kittlesen, and Y. S. Hahn (1999)
J. Immunol. 162, 931-938
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Complement-dependent Clearance of Apoptotic Cells by Human Macrophages.
D. Mevorach, J. O. Mascarenhas, D. Gershov, and K. B. Elkon (1998)
J. Exp. Med. 188, 2313-2320
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Early childhood infection and atopic disorder.
I S. Farooqi and J. M Hopkin (1998)
Thorax 53, 927-932
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Measles Virus Spread and Pathogenesis in Genetically Modified Mice.
B. Mrkic, J. Pavlovic, T. Rulicke, P. Volpe, C. J. Buchholz, D. Hourcade, J. P. Atkinson, A. Aguzzi, and R. Cattaneo (1998)
J. Virol. 72, 7420-7427
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IFN-{alpha} Priming of Human Monocytes Differentially Regulates Gram-Positive and Gram-Negative Bacteria-Induced IL-10 Release and Selectively Enhances IL-12p70, CD80, and MHC Class I Expression.
P. Hermann, M. Rubio, T. Nakajima, G. Delespesse, and M. Sarfati (1998)
J. Immunol. 161, 2011-2018
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Deficiency of the Humoral Immune Response to Measles Vaccine in Infants Immunized at Age 6 Months.
H. A. Gans, A. M. Arvin, J. Galinus, L. Logan, R. DeHovitz, and Y. Maldonado (1998)
JAMA 280, 527-532
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