Morphine has a profound effect on the immune system by its ability to prevent development of cell-mediated immune responses against intracellular pathogens. The effect has three important implications for the pathogenesis of HIV infection, especially NeuroAIDS. First, it modifies the receptor used by the virus to infect macrophages and this potentially causes enhancement of infection in these cells. Since macrophages are the main cells in the brain that support replication of the virus, the effect of morphine would be to enhance the infection in the brain. The second implication is that morphine-mediated suppression of production of IFN3 would abolish anti-HIV CMI responses, the major arm of the immune system responsible for controlling replication of the virus. Loss of CMI would therefore predict continuous and more robust replication of the virus in the brain. Finally, cessation of morphine intake results in recovery of the immune system and therefore, reconstitution of the potential to mount CMI responses. Such an occurrence in the HIV infected individual would result in reconstitution of the antiviral CMI response in brains that have large amounts of viral antigen. This could result in severe encephalitis. We will use the Morphine-SIV-Macaque model to explore these concepts. Our hypothesis is that morphine will cause a non-inflammatory, continuous build up of SIV in the brains of infected macaques, with a prognosis for more rapid progression to development of encephalitis than non-treated infected animals, and that onset of this syndrome would be accelerated following withdrawal of the drug from infected, chronically exposed animals. Epidemiological studies on HIV-infected persons addicted to opioids have led to controversial conclusions. Some studies show that morphine worsens the infections, while others claim amelioration of the infection. The SIV-Macaque-Model of HIV pathogenesis will be used to explore the mechanisms of this drug on infection in the brain.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA024442-06
Application #
8132888
Study Section
Special Emphasis Panel (ZDA1-NXR-B (20))
Program Officer
Lawrence, Diane M
Project Start
2007-09-30
Project End
2013-08-31
Budget Start
2011-09-01
Budget End
2013-08-31
Support Year
6
Fiscal Year
2011
Total Cost
$427,818
Indirect Cost
Name
University of Nebraska Medical Center
Department
Pharmacology
Type
Schools of Medicine
DUNS #
168559177
City
Omaha
State
NE
Country
United States
Zip Code
68198
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