Filovirus Entry: A Novelty in the Viral Fusion World

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

The cellular uptake pathways mediating filovirus entry remain controversial despite numerous studies. The three most common and well studied endocytic pathways-caveolin-dependent endocytosis, clathrin-dependent endocytosis and macropinocytosis-have all been implicated in filovirus entry. Early studies reported that the caveolae vesicular system and/or lipid raft domains were important for EBOV GP-mediated entry [65] [66] [67] . However, it was demonstrated that overexpression of Caveolin 1 in the poorly permissive lymphocytic cell line CEM did not enhance levels of EBOV GP-dependent transduction, suggesting that caveolae may not play a role in filovirus entry [36] . Since that time several groups have also implicated clathrin-dependent entry mechanisms in filovirus entry [68] [69] [70] [71] . In parallel, other groups using virus-like particles (VLPs) and/or infectious filovirions identified macropinocytosis as a main and perhaps sole mechanism of filovirus uptake [62, 63] . Several groups have found that EBOV GP-dependent entry can occur through a variety of different uptake mechanisms including caveolae, clathrin-coated pits and through actin-and microtubule-dependent pathways such as macropinocytosis [61, 70, 71] within the same cell population.