Eliseo Eugenin. PhD
THE PUBLIC HEALTH RESEARCH INSTITUTE CENTER
at the International Center for Public Health (ICPH)
Department of Microbiology and Molecular Genetics
Rutgers Medical School
Novel mechanism of HIV brain disease
Eliseo A. Eugenin1,2,*. Public Health Research Institute (PHRI) and 2Department of Microbiology and Molecular Genetics, Rutgers University, Newark, NJ, USA.
HIV entry into the central nervous system (CNS) is an early event after infection, resulting in neurological dysfunction in a significant number of individuals. As people with AIDS live longer, the prevalence of cognitive impairment is increasing, despite antiretroviral therapy. The mechanisms that mediate CNS dysfunction are still not well understood, but are postulated to be a combination of inflammation, and viral infection and/or replication. In addition to those mechanisms, we recently demonstrated that HIV infection of astrocytes mediated survival of HIV infected cells and bystander killing of surrounding uninfected cells by a mechanism that is gap junction and hemichannel dependent. We now characterize the mechanisms of HIV mediated protection of infected astrocytes with an emphasis on mitochondrial dysregulation and identification of the intracellular factors that mediate bystander killing of uninfected cells. Our findings describe a novel mechanism by which HIV maintains survival of HIV infected astrocytes and we identify IP3, calcium and Cytochrome C as key signals involved in bystander killing of uninfected cells in contact with HIV infected astrocytes by a gap junction and hemichannel dependent mechanism. Thus, our data provide novel mechanisms of HIV survival and toxicity in the current NeuroAIDS era, where viral replication is not a major component due to effective antiretroviral treatments. Our findings identify new potential therapeutic targets to reduce the devastating consequences of NeuroAIDS.
My expertise is in glial function (astrocytes and microglia), CNS pathology and HIV. Our laboratory has demonstrated a successful and productive research in Neuro-virological diseases, such as HIV associated neuropathologies, cell to cell communication, synapses, glial biology and substance abuse. In addition, my laboratory has been a leader in the examination of electrical synapses in several CNS diseases including stroke, NeuroAIDS and encephalitis. In addition, I am part of the PHRI imaging facilities http://phri.org/facilities/facil_imaging.asp.