Science Daily (05.01.2013)
HIV hides within certain types of cells and reproduces slowly, eventually causing chronic inflammation regardless of drug treatment. According to Servio H. Ramirez PhD, assistant professor of pathology and laboratory medicine at Temple University School of Medicine (TUSM), although antiretroviral drugs allowed persons with HIV infection to live longer, the patients continue to have extended exposure to low levels of HIV replication and associated inflammation. It is believed that this inflammatory process in the central nervous system (CNS) is the underlying cause of HIV-associated neurocognitive disorder.
Researchers at TUSM’s Department of Pathology and Laboratory Medicine and Center for Substance Abuse Research investigated the connection between inflammation and neurocognitive conditions linked to long-term HIV exposure. Ramirez and colleagues focused on the CB2 receptor, a protein located on the surface of macrophages. Macrophages are a type of white blood cell that engulfs and destroys foreign agents, and the researchers believed they are likely the primary reservoir for HIV. They are the first cells infected after sexual transmission of the virus, are found in every organ of the human body, and circulate in the blood. They believe that macrophages may be carrying HIV into the brain, and initiating HIV-associated cognitive decline.
CB2 is a binding site for cannabinoids, active compounds of cannabis (marijuana), but does not transmit the psychoactive effects of cannabis. The researchers hypothesized that CB2 may play a role in blocking inflammation in the CNS. They discovered that synthetic anti-inflammatory substances distantly related to the active ingredient in marijuana may take the strength out of HIV while the virus is hiding in macrophages. The researchers conducted experiments using a non-clinical HIV macrophage cell model. They treated the HIV-infected cells with one of three different synthetic CB2-activating compounds and sampled the cells periodically to measure the activity of the enzyme called reverse transcriptase, which is essential for HIV replication. After seven days, all three compounds had successfully attenuated HIV replication.
Results suggest that selective CB2 agonists could potentially be used along with antiretroviral drugs to create new HIV/AIDS drug treatments and that the human immune system could be enhanced to fight HIV. Yuri Persidsky, MD, PhD, chair of TUSM’s Department of Pathology and Laboratory Medicine and one of the researchers, commented that the study suggests that stimulating CB2 receptors in white blood cells could produce benefits against other viral infections.
The full article, “Attenuation of HIV-1 Replication in Macrophages by Cannabinoid Receptor 2 Agonists,” was published in the Journal of Leukocyte Biology (2013; 93 (5):801–810).