AIDS and the brain: is there a chemokine connection?

Abstract

Many HIV-1-positive individuals suffer from a variety of neurological problems known collectively as the HIV-1-related cognitive-motor complex. However, the molecular mechanisms that underlie HIV-1-induced neuropathology are unclear. They might include a combination of indirect effects, which result from the release of neurotoxins from activated astrocytes and microglia, and the direct effects of HIV-1-related proteins, such as gp120, on neurons. As the interaction of gp120 with immune cells has been shown to require the participation of chemokine receptors, this article explores the possibility that such receptors participate in the events underlying HIV-1-induced neuropathology. It is now clear that many types of cell in the brain possess chemokine receptors, including microglia, glia and neurons, and the interaction of gp120 with neuronal chemokine receptors initiates apoptotic death of neurons in vitro. Such effects might be modified by the actions of chemokines that act at these same receptors. However, the importance of this direct interaction with neurons in vivo and its relevance in the pathogenesis of AIDS-related dementia still needs to be established. Furthermore, the existence of chemokine receptors on neurons suggests that chemokines might regulate neuronal functions physiologically.