Ebola and Marburg viruses cause outbreaks of highly lethal infection in central Africa. In the last few years, rapid progress has been made in understanding how these viruses are transmitted and spread. These studies show that the glycoprotein GP that protrudes from the virus envelope mediates membrane fusion and infection. Activation of the GP membrane fusion activity is triggered by a multi-step pathway initiated by binding to lectins expressed on the cell surface. After uptake of lectin-bound particles by macropinocytosis, virus-containing vesicles are transported to late endosomes and lysosomes containing the protease cathepsin B and the membrane protein Niemann-Pick C1 (NPC1), which are essential for infection. Recent studies indicate that cathepsin B cleaves GP, removing heavily glycosylated sequences and exposing the domain in GP that is a ligand for NPC1. Although more studies are needed, current evidence strongly suggests that binding of protease-cleaved GP to NPC1 is the signal that activates virus membrane fusion and infection. Importantly, small molecules that target NPC1 and interfere with GP binding and ebolavirus infection have been identified. A major goal is to develop these inhibitors into anti-viral drugs.
Keywords: Niemann-Pick C1; cathepsins; cellular factors; filovirus; macropinocytosis.