Filovirus Entry: A Novelty in the Viral Fusion World

Hunt, Catherine L.; Lennemann, Nicholas J.; Maury, Wendy

NPC1 is primarily a membrane bound, late endosomal/lysosomal protein that is critical for cholesterol absorption and homeostasis. Those individuals lacking a functional NPC1 exhibit an abnormally high accumulation of cholesterol in the lysosomes of their cells, leading to altered protein and lipid trafficking with most cases resulting in fatality by 18 months of age [85] . Cells where NPC1 function has been biochemically disrupted or cells lacking NPC1 showed a resistance to EBOV infection [83, 84] . Clearance of cholesterol from NPC1 null cells by cultivation in lipoprotein-depleted media did not rescue EBOV infection, indicating that the NPC1 protein itself, and not aberrant cholesterol transport, was important for EBOV entry [84] . Cote et al. also showed that the expression of NPC1 and not its cholesterol transport activity were critical for EBOV entry [83] .