Filovirus Entry: A Novelty in the Viral Fusion World

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

A number of these uptake studies that identified caveolin and/or clathrin as important in entry used EBOV GP pseudotyped lentiviruses or vesicular stomatitis virus (VSV) as the cargo and an argument has been made that these smaller viral particles do not accurately represent the size constraints that may limit the uptake options of a filovirion that can be greater than 10 µM in length [72] . While a role for caveolin-and clathrin-dependent pathways in infectious filoviral entry remains to be demonstrated, it should be noted that several large, intracellular bacteria or parasites have been found to use either caveolin-or clathrin-dependent pathways, suggesting that the size of these vesicles can be expanded to meet the size of the cargo [73] [74] [75] . In addition, it is likely that the mechanism of EBOV uptake may be cell-dependent as both Green African Monkey cells (Vero) [62, 63] and human neuroblastoma cells (SNB-19) [61] both primarily use macropinocytosis for EBOV uptake. However, the signaling pathways that are required for virus entry is cell-specific since Vero cells require activation of the PI3K/Akt pathway, whereas SNB-19 cells require PLC activation [61] .