Measles virus (MV) is an important pathogen that remains a worldwide health problem both in developing countries as well as in the United States and Europe. MV causes approximately 1.5 to 2 million deaths per year, primarily in children under 5 years of age. One of the characteristics of measles virus infections is prolonged abnormalities of cell-mediated immunity (CMI) which results in immunosuppression and is thought to contribute to the increased susceptibility to secondary infections which is primarily responsible for most of the morbidity and mortality of the disease. The underlying mechanism(s) responsible for this immunosuppression is not known. Interleukin 12 (IL-12) is an important regulator of the cell-mediated response which is produced primarily by monocytes/macrophages. It has been shown that in vitro infection of monocytes with MV specifically downregulates production of IL-12. Similar effects on IL-12 production are seen when CD46, a complement regulatory protein and the cellular receptor for MV, is crosslinked either by antibody, polymerized C3b (an endogenous complement ligand for CD46), or with transiently expressed MV hemagglutinin. These finding provide a plausible mechanism for the MV-induced suppression of CMI. This proposal will test the hypothesis that the utilization of CD46 by MV results in suppression of CMI through the inhibition of IL-12 production. The goals are to define the mechanism(s) of CD46-mediated suppression of IL-12 production, and to characterize IL-12 responses in perpherial blood mononuclear cells from patients with measles.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
7R29AI040507-04
Application #
6170102
Study Section
Virology Study Section (VR)
Program Officer
Meegan, James M
Project Start
1997-08-01
Project End
2002-07-31
Budget Start
2000-09-01
Budget End
2001-07-31
Support Year
4
Fiscal Year
2000
Total Cost
$106,018
Indirect Cost
Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229
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Karp, C L (1999) Measles: immunosuppression, interleukin-12, and complement receptors. Immunol Rev 168:91-101
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