The goal of this study is to examine the role of the cytokine system in the murine retroviral-induced immunodeficiency syndrome (MAIDS). We will determine whether retroviral infection alters the regulated expression of cytokines connected with the interferon system and whether an alteration in the synthesis of these regulatory polypeptides contributes to the pathophysiology of retroviral infection. Striking similarities between the symptoms of viral-induced immunodeficiency in patients with AIDs and its mouse counterpart, MAIDS, were recently shown. These include deficiencies in both T- and B-cell responses to mitogenic and antigenic stimuli, decreased ability to synthesize alpha- interferons, production of an acid-labile interferon, enhanced susceptibility to infection, and evolution of B-cell lymphomas. In the present proposal, we shall use the murine AIDS model to examine the following questions: 1) What is the role of the interferon system in the induction of MAIDS associated symptoms? Is the inhibition of interferon inducibility due to the viral infection of the producing cells or altered cytokine production? Does the constitutive expression of the gamma-interferon gene in these mice contribute to some of the observed alterations in the immune system? 2) Are the abnormalities of this immunodeficient syndrome associated with the virus-induced alteration of synthesis of various lymphokines or cytokines? Does viral infection alter the expression of different cytokines in monocyte/macrophage lineage cells and T-cells? Is this alteration virus specific and can it be demonstrated during infection in vitro? 3) What is the molecular mechanism by which virus infection alters the expression of cytokine genes? We believe that the MAIDS will allow us to study in molecular terms the complex mechanisms of virus-cell interaction and virus-induced immunosuppression, and will provide us with a firm foundation for understanding the effects of retrovirus infection in man, such as AIDS.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA050158-03
Application #
3194461
Study Section
Special Emphasis Panel (SRC (56))
Project Start
1989-03-15
Project End
1994-02-28
Budget Start
1991-03-01
Budget End
1992-02-29
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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