This study aims to better understand the mechanisms by which Ebola virus infects cells and causes disease. To better understand the mechanisms by which Ebola virus infects cells and causes disease. Our laboratory is interested the basic biology underlying Ebola virus pathogenesis, virus-host interactions, and inhibition of virus replication. Ebola virus is a non-segmented negative strand RNA virus with a simple genome containing seven open reading frames. The virus replication cycle begins with binding of the envelope glycoprotein, GP, to a putative cell surface receptor(s) and entry into the host cell by fusion of viral and cell membranes. Strategies to interrupt the virus life cycle can be targeted to these early entry events or to later steps in the replication cycle. Our hypothesis is that molecular events underlying Ebola GP interactions within the host contribute to preferential targeting of Ebola virus infection to specific cell types, mediate pathogenic properties of the virus, and influence immune responses generated against the virus. Our goal with these studies is to identify points in the Ebola virus replication cycle that are vulnerable antiviral and neutralization targets. We are approaching this goal with several aims, each focusing on a particular aspect of GP function. In the scenario of an outbreak, people are not diagnosed with Ebola virus until they are already sick, at which point vaccinations are typically not helpful and a post exposure therapeutic is needed. We have isolated and characterized a panel of monoclonal antibodies that show potent neutralizing activity in vitro and these will be tested for in vivo efficacy using the rhesus macaque challenge model for Ebola Zaire or Sudan.