Cellular Communication

Role of cellular communication through gap junctions, tunneling nanotubes, hemichannels and ATP receptors during the pathogenesis of NeuroHIV

Human immunodeficiency virus (HIV) infection of the central nervous system (CNS) can result in neurologic dysfunction with devastating consequences in a significant number of individuals with acquired immunodeficiency syndrome (AIDS). The major CNS complications in individuals with HIV are encephalitis, dementia and/or cognitive impairment that are characterized by leukocyte infiltration into the CNS, microglia activation, aberrant chemokine expression, blood brain barrier (BBB) disruption, and eventual damage and/or loss of neurons. As the HIV-infected population lives longer, an understanding of the impact of the virus on chronic disease processes such as NeuroHIV becomes increasingly relevant. NeuroHIV has been associated with the presence of elevated CNS inflammatory factors, such as cytokines, PAF, excitatory aminoacids (especially glutamate) and their receptors, soluble viral proteins, and chemokines, as determined in post-mortem examination of tissue. These observations in vivo have been correlated with in vitro findings that support the participation of these factors as mediators of neurodegeneration. The mechanism that triggers these abnormalities are not always associated with high viral replication but rather with inflammation. To study the development of NeuroHIV we examine two different, but interrelated, potential mechanisms of pathogenesis.

Our focus is to examine the role of HIV infection of astrocytes in the pathogenesis of NeuroHIV as well as in immune cells, macrophages and T cells, with special emphasis in the role of gap junction channels, hemichannels of pannexins and connexin, ATP receptors and a new system of communication named tunneling nanotube (TNT). We examined how these systems amplify inflammation and toxicity and how these communication systems are altered by HIV infection in vitro and in vivo. These studies are essential to understand the mechanism by which HIV remains in the brain, as a reservoir of the virus, and to explore the question of how HIV changes the phenotype of HIV-infected cells to its advantage.